betadex and gamma-cyclodextrin

Cyclodextrin (CD)-metal-organic frameworks (MOFs) are developed as a new type of food-acceptable multi-porous material, which shows a great potential for controlled volatile compound release. This study aimed to synthesize CD-MOFs from potassium nitrate, crystallized with α-cyclodextrin (α-CD), β-CD or γ-CD, and their complex capacities were further evaluated using menthol encapsulation. Compared with CD, all the CD-MOFs had highly ordered crystal structures and more regular shapes. β-CD-MOF showed better thermal stability, with an initial thermal degradation temperature of 253 °C, higher than the other two CD-MOFs. The CD-MOFs were used for menthol encapsulation and the resulting menthol concentration within the inclusion complexes (ICs) was determined. The menthol concentration in ICs followed the order: β-CD-MOF > β-CD > γ-CD-MOF > γ-CD > α-CD ≥ α-CD-MOF. The menthol content and encapsulation efficiency of β-CD-MOF were 21.76% (w/w) and 22.54% (w/w) respectively, significantly higher than those of other reported solid materials, such as amylose, CD and V-type starch.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Crystallography, X-Ray; Cyclodextrins; gamma-Cyclodextrins; Menthol; Metal-Organic Frameworks; Porosity; Spectroscopy, Fourier Transform Infrared; Temperature; Thermogravimetry

Over the years, cyclodextrin uses have been widely reviewed and their proprieties provide a very attractive approach in different biomedical applications. Cyclodextrins, due to their characteristics, are used to transport drugs and have also been studied as molecular chaperones with potential application in protein misfolding diseases. In this study, we designed cyclodextrin polymers containing different contents of β- or γ-cyclodextrin, and a different number of guanidinium positive charges. This allowed exploration of the influence of the charge in delivering a drug and the effect in the protein anti-aggregant ability. The polymers inhibit Amiloid β peptide aggregation; such an ability is modulated by both the type of CyD cavity and the number of charges. We also explored the effect of the new polymers as drug carriers. We tested the Doxorubicin toxicity in different cell lines, A2780, A549, MDA-MB-231 in the presence of the polymers. Data show that the polymers based on γ-cyclodextrin modified the cytotoxicity of doxorubicin in the A2780 cell line.

Topics: A549 Cells; beta-Cyclodextrins; Cellulose; Cyclodextrins; Doxorubicin; Drug Carriers; gamma-Cyclodextrins; Humans; Neoplasms

This work investigated the interaction between cyclodextrins and pullulanase to provide insight into the production and application of cyclodextrins. Enzyme activity and kinetic assays showed that α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) inhibited pullulanase in a competitive manner. Circular dichroism spectra and fluorescence spectroscopy suggested the formation of cyclodextrin and pullulanase complexes. According to ITC assays and molecular docking results, compared with α-CD and γ-CD, β-CD had the strongest affinity for pullulanase because of its appropriate cavity geometric dimensions. In addition, cyclodextrins interacted with pullulanase through hydrogen bonds, van der Waals force and hydrophobic interactions, the latter of which were verified as the major driving force. Phenylalanine 476 was the key amino acid residue in pullulanase for cyclodextrin recognition and binding.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Calorimetry; Circular Dichroism; Cyclodextrins; gamma-Cyclodextrins; Glycoside Hydrolases; Hydrogen Bonding; Molecular Docking Simulation; Phenylalanine; Protein Structure, Secondary; Spectrometry, Fluorescence

The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood-brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied. The stoichiometry, binding constant, enthalpy, and entropy of complex formation between CPZ and a panel of CDs was investigated by isothermal titration calorimetry (ITC). All the tested CDs were able to include CPZ, in the form of 1:1, 1:2 or a mixture of 1:1 and 1:2 complexes. In particular, a substituted γ-CD, sugammadex (the octasodium salt of octakis(6-deoxy-6-S-(2-carboxyethyl)-6-thio)cyclomaltooctaose), formed exclusively 1:2 complexes with an extremely high association constant of 6.37 × 10

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Chlorpromazine; Cyclodextrins; Delayed-Action Preparations; Drug Carriers; Drug Repositioning; Drug Stability; gamma-Cyclodextrins; Liposomes; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Sugammadex; Thermodynamics

NMR spectroscopy is used to investigate the host-guest complexation of (R)-tedizolid, such as tedizolid with the hydroxymethyl substituent at the C5 position of the oxazolidinone ring ((R)-TED) or tedizolid with 5-methyl dihydrogen phosphate ((R)-TED-PO

Topics: beta-Cyclodextrins; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Oxazolidinones; Stereoisomerism; Tetrazoles

The interaction of a cationic photosensitizer Safranin-O with liposome membranes having similar surface charge (negative) but differing in the presence of saturation on the lipid side-chain has been studied. To this end, dimyristoyl-l-R-phosphatidylglycerol (DMPG) and 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG) phospholipids were employed to prepare small unilamellar vesicles. The dye is found to bind in the headgroup region of both the liposome membranes with significantly higher affinity to DOPG lipid containing unsaturated side chain. The effects of various cyclodextrins (CDs) on the stability of the probe-bound liposome membranes have also been investigated using steady-state and picosecond-resolved fluorescence as well as dynamic light scattering techniques. The modulations of the fluorescence properties of the lipid-bound dye were exploited to rationalize the membrane destabilization following interaction with the cyclodextrins. Experimental results reveal the selective interaction of DMPG membrane with CDs leading to rupture of the integrated structure of the liposome units accompanying release of the bound probe to the bulk aqueous phase. On the contrary, no discernible interaction of the CDs was observed with DOPG liposome membrane. Our results also show the differential extents of interaction of various CDs (α-CD, β-CD, methyl-β-CD, and γ-CD) with DMPG leading to varying degrees of release of the bound-dye molecule.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Drug Liberation; gamma-Cyclodextrins; Kinetics; Phenazines; Phosphatidylglycerols; Photosensitizing Agents; Solutions; Spectrometry, Fluorescence; Static Electricity; Unilamellar Liposomes

In comparison with natural α- and β-cyclodextrin (CD), γ-CD has attracted much attention due to their large hydrophobic cavities, high water solubility, and bioavailability. However, the production of γ-CD is still rather expensive and time-consuming. To overcome the high cost and long induction time, pUC119 was selected as the gene expression vector, and the recombinant enzyme production time was reduced to 8h from 72h. Furthermore, for the first time, we have successfully produced γ-CD using β-CD by cyclodextrin opening reactions through the recombinant CGTase in the presence of maltose. The kinetic mechanism of the coupling reaction was investigated. Moreover, the production of γ-CD could be affected by several key parameters, such as solvent type, reaction time, pH, and temperature. A maximum γ-CD yield of 32.9% was achieved by recombinant CGTase in the presence of 5-cyclohexadecen-1-one. This could be a promising method for the industrial production of γ-CD.

Topics: beta-Cyclodextrins; gamma-Cyclodextrins; Glucosyltransferases; Kinetics; Recombinant Proteins

Topics: Aldehydes; alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Food Storage; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Phospholipases A2; Phospholipids; Solubility; Soybean Proteins; Taste; Temperature

Determination of organic pollutants in environmental samples presents great difficulties due to the lack of sensitivity and selectivity in many of the existing analytical methods. In this work, the efficiency of materials based on silica structures containing bounded γ-cyclodextrin has been evaluated to determinate phenolic compounds and polycyclic aromatic hydrocarbons in air and water samples, respectively, in comparison with materials made of β-cyclodextrin. According to the results obtained for the material characterization, the new γ-cyclodextrin solid phase does not apparently present any porosity when used in air samples, but it has been shown to work efficiently for the preconcentration of polycyclic aromatic hydrocarbons in water, with recoveries around 80%. In addition, the use of the β-cyclodextrin material for phenolic compounds sampling can be highlighted with recoveries between 83% and 95%, and recoveries for 4-vinylphenol and 2-methoxy-4-vinylphenol have been especially improved in comparison with the use of materials containing trapped β-cyclodextrin in our previous researches. The observed phenomena can be explained on the basis of the analyte molecules size and the diameter of the cyclodextrin cavities, the influence of the cyclodextrin type in the material structure as well as on the interactions taking place with the pollutants and the influence of the matrix type in the retention and desorption mechanisms.

Topics: Air Pollutants; beta-Cyclodextrins; gamma-Cyclodextrins; Gas Chromatography-Mass Spectrometry; Limit of Detection; Polycyclic Aromatic Hydrocarbons; Porosity; Silicon Dioxide; Solid Phase Extraction; Water Pollutants, Chemical

A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π≥90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5cm; temperature, 18°C; voltage, 26kV (26-27kV); background electrolyte, 150mM phosphate buffer pH 2.70 (2.60-2.80), 3.1mM (3.0-3.5mM) HPγCyD; 2.00% (0.00-8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets.

Topics: beta-Cyclodextrins; Cinacalcet; Drug Contamination; Electrophoresis, Capillary; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Monte Carlo Method; Probability; Risk Assessment; Solvents; Stereoisomerism

The chiral lactone 5-butyl-4-methyloxolan-2-one or 5-butyl-4-methyldihydro-2(3H)-furanone, often named whisky lactone, is found in oak wood, then contributing to the appreciated flavor of beverages stored in such wooden barrels. Its next higher homologue is named cognac lactone (5-pentyl-4-methyloxolan-2-one or 5-pentyl-4-methyldihydro-2(3H)-furanone), however is much less known, probably due to its minor concentration level. In order to study the direct enantioseparation of both lactones by gas chromatography on chiral stationary phases, individual enantiomers, particularly for cognac lactone were made available. This was achieved by baker's yeast reduction of synthesized ethyl 3-methyl-4-oxononanoate or, after hydrolysis, of the corresponding 4-ketoacid, that gave access to individual enantiomers of cognac lactone. Good enantioseparation was achieved for both whisky and cognac lactone with high values for the chiral resolution with 6-O-tert. butyl dimethylsilyl-2,3-dialkylated or 6-O-tert. butyl dimethylsilyl-2,3-diacylated cyclodextrin derivatives as chiral selectors. The influence of the nature and position of derivatization of the cyclodextrin moiety revealed a strong impact on the chiral recognition mechanism, as the investigated alkylated derivatives heptakis-(2,6-di-O-iso-pentyl-3-O-allyl)-β-cyclodextrin and octakis-(2,3-di-O-pentyl-6-O-methyl)-γ-cyclodextrin did not provide any or only minor chiral selectivity for the two lactones.

Topics: Alcoholic Beverages; beta-Cyclodextrins; Chemistry Techniques, Analytical; Chromatography, Gas; Cyclodextrins; gamma-Cyclodextrins; Lactones; Stereoisomerism

We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host-guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host-guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV.

Topics: Adamantane; beta-Cyclodextrins; Calorimetry; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Mannose; Nanodiamonds; Nanostructures; Optical Rotation; Thermodynamics

Small molecule drug activators of gene expression have been used in applications ranging from gene therapy, to tissue engineering and regenerative medicine. One concern is that for sustained gene expression, a long-term, controlled delivery system is needed. Insoluble polymers containing a high proportion of cyclodextrin (CD) affinity groups have been shown to prolong drug delivery far beyond that capable of polymers relying on diffusion alone. In this study we evaluate the capacity of such polymers to deliver the transgene inducer doxycycline. Our results show that initial drug loading is proportional to affinity, with ∼8% loading in high-affinity γ-CD polymers; ∼7% loading in moderate-affinity β-CD polymers; and only ∼4.5% loading in the non-affinity control polymer made from linear dextran. When release aliquots from these polymers were incubated with cells genetically modified for inducible transgene expression we observed activation of transgene expression for up to three weeks from samples released by affinity-based polymers. We showed that drug stability is maintained over the course of the study using a bacterial zone of inhibition assay where again affinity-based polymers show sustained availability of drug, weeks longer than non-affinity controls. Lastly we provide theoretical calculations of strength of binding interactions between cyclodextrins and many additional transgene inducers demonstrating the broad utility of this delivery platform.

Topics: beta-Cyclodextrins; Delayed-Action Preparations; Dextrans; Doxycycline; Drug Delivery Systems; gamma-Cyclodextrins; Gene Expression; Green Fluorescent Proteins; Humans; MCF-7 Cells; Models, Molecular; Transgenes

Permeation techniques can be applied to determine the critical aggregation concentration (cac) of natural cyclodextrins (CDs) in aqueous solutions although the method is both laborious and time consuming. In the present study, the permeation technique was modified and the influence of osmotic pressure, sampling time, CD concentration and molecular weight-cut off (MWCO) of the membrane were investigated in two different permeation units, that is Franz diffusion cells and Slide-A-Lyzer™ MINI Dialysis. While both the osmotic pressure and CD concentration affect the steady state flux in both permeation units, effects of sampling time and the MWCO of the mounted membrane were only observed in the Franz diffusion cells. The osmotic effect was negligible in the Slide-A-Lyzer™ MINI Dialysis units. The modified permeation technique using Slide-A-Lyzer™ MINI Dialysis units was then used to determine the cac of natural CDs in water. The cac of αCD, βCD and γCD was 1.19±0.17, 0.69±0.05 and 0.93±0.04% (w/v), respectively. The results indicated that the cac values depended on their intrinsic solubility. Moreover, the cac value of γCD in aqueous hydrocortisone/γCD inclusion complex solution was identical to the γCD cac value determined in pure water.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chemistry, Pharmaceutical; Excipients; gamma-Cyclodextrins; Hydrocortisone; Molecular Weight; Osmotic Pressure; Permeability; Solubility

The objectives were to examine in vitro fermentation characteristics, in vivo nutrient digestibility, fecal microbiota, and serum lipid profiles as affected by α-cyclodextrin (ACD) supplementation. Short-chain fatty acid (SCFA) production was measured after in vitro fermentation for 3, 6, 9, and 12 h of ACD, β-cyclodextrin, and γ-cyclodextrin. Five mixed-breed hounds were used in a Latin square design. Each experimental period comprised 14 d, including 10 d for diet adaptation and 4 d for fecal collection. Dogs were fed, twice a day, an extruded diet made with poultry byproduct meal and brewer's rice as the main ingredients. Dogs were supplemented with 0, 1, 2, 3, or 4 g of ACD diluted in 15 mL of water twice daily for a total of 0, 2, 4, 6, and 8 g ACD/d. Maximal in vitro production of total SCFA was lowest for ACD. However, the greatest maximal production of propionate was noted for ACD treatment. Total tract nutrient digestibility and fecal DM concentration linearly decreased ( < 0.05) for treatment groups receiving ACD; no changes were observed for ileal digestibility. Serum cholesterol and triglyceride concentrations were within normal ranges for dogs and were not different among treatments. Similarly, no changes in fecal microbiota were observed. Overall, ACD supplementation appears to have no effect on nutrient absorption in the small intestine but may alter fermentation in the large bowel, which could lead to a higher proportion of propionate production as observed in the in vitro experiment.

Topics: alpha-Cyclodextrins; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; beta-Cyclodextrins; Diet; Dietary Supplements; Digestion; Dogs; Dose-Response Relationship, Drug; Fatty Acids, Volatile; Feces; Fermentation; gamma-Cyclodextrins; Gastrointestinal Tract; Microbiota

The fabrication and development of two polyvinyl chloride (PVC) membrane sensors for assaying phenobarbitone sodium are described. Sensors 1 and 2 were fabricated utilizing β- or γ-cyclodextrin as ionophore in the presence of tridodecylmethylammonium chloride as a membrane additive, and PVC and dioctyl phthalate as plasticizer. The analytical parameters of both sensors were evaluated according to the IUPAC guidelines. The proposed sensors showed rapid, stable anionic response (-59.1 and -62.0 mV per decade) over a relatively wide phenobarbitone concentration range (5.0 × 10-6-1 × 10-2 and 8 × 10-6-1 × 10-2 mol L-1) in the pH range of 9-11. The limit of detection was 3.5 × 10-6 and 7.0 × 10-6 mol L-1 for sensors 1 and 2, respectively. The fabricated sensors showed high selectivity for phenobarbitone over the investigated foreign species. An average recovery of 2.54 μg mL-1 phenobarbitone sodium was 97.4 and 101.1 %, while the mean relative standard deviation was 3.0 and 2.1 %, for sensors 1 and 2, respectively. The results acquired for determination of phenobarbitone in its dosage forms utilizing the proposed sensors are in good agreement with those obtained by the British Pharmacopoeial method.

Topics: Anticonvulsants; beta-Cyclodextrins; Biosensing Techniques; Calibration; Chemistry, Pharmaceutical; Diethylhexyl Phthalate; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Indicators and Reagents; Ionophores; Limit of Detection; Membrane Potentials; Membranes, Artificial; Pharmaceutical Solutions; Phenobarbital; Plasticizers; Polyvinyl Chloride; Quaternary Ammonium Compounds; Reproducibility of Results; Tablets

Inclusion complexes of estragole (ES) as pure compound and as main component of basil and tarragon essential oils (EOs) with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB), a low methylated-β-cyclodextrin (CRYSMEB) and γ-cyclodextrin (γ-CD) were characterized. Formation constants (Kf) of the complexes were determined in aqueous solution by nonlinear regression analysis using static headspace gas chromatography (SH-GC) and UV-visible spectroscopy. Solid inclusion complexes were prepared by the freeze-drying method for different CD:ES molar ratios and were characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). Inclusion complexes formation allowed the controlled release of ES. Moreover, increased DPPH radical scavenging activity and photostability of ES and ES containing EOs (ESEOs) were observed in the presence of CDs. These findings suggest that encapsulation with CDs could be an efficient tool to improve the use of ES and ESEOs in aromatherapy, cosmetic and food fields.

Topics: Allylbenzene Derivatives; alpha-Cyclodextrins; Anisoles; Artemisia; beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclodextrins; gamma-Cyclodextrins; Ocimum basilicum; Oils, Volatile; Spectroscopy, Fourier Transform Infrared

Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using multiple cyclodextrin derivatives. The known propensity of the cyclodextrins to bind hydrophobic guests in their hydrophobic interiors enhanced the extraction of aromatic analytes from the oil layer to the aqueous layer, with methyl-β-cyclodextrin and β-cyclodextrin providing the most significant enhancement in extraction efficiencies of aromatic toxicants (69% aromatic toxicants in aqueous layer in the presence of methyl-β-cyclodextrin compared to 47% in cyclodextrin-free solution for tar ball oil extraction), and provide optimal tunability for developing efficient extraction systems. The cyclodextrin derivatives also promoted efficient energy transfer in the aqueous solutions, with up to 86% efficient energy transfer observed in the presence of γ-cyclodextrin compared to 50% in the absence of cyclodextrin for oil spill oil extraction. Together, this dual function extraction followed by detection system has potential in the development of environmental remediation systems.

Topics: beta-Cyclodextrins; Cyclodextrins; Energy Transfer; Environmental Restoration and Remediation; gamma-Cyclodextrins; Hazardous Substances; Petroleum; Petroleum Pollution; Spectrometry, Fluorescence; Water Pollutants, Chemical

"Cyclodextrin-gas" clathrates were obtained by crystallization from water solution of α-, β-, and γ-cyclodextrins (CDs) under pressure of the gas to be entrapped into the CD molecules. When the pressure is released, these clathrates are stable at ambient conditions and dissociate at elevated temperature, which makes them interesting for various applications as foam boosters in food and other industries. It was found that under these conditions α-CD forms clathrates with all of the gases used in this study (N2, N2O, CO2, Ar), whereas β- and γ-CDs can form clathrates only with N2. The concentration of the cyclodextrin and the temperature and pressure of the gas were varied for achieving higher clathrate yield and larger amount of embedded gas. Highest values of about 2 wt % were found for α-CD-N2O, as it releases in the temperature range of 40-60 °C.

Topics: alpha-Cyclodextrins; Argon; beta-Cyclodextrins; Carbon Dioxide; Crystallization; Cyclodextrins; Drug Stability; gamma-Cyclodextrins; Gases; Nitrogen; Nitrous Oxide; Pressure; Temperature

Complexes of ethyl butyrate and hexanal encapsulated by β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) were prepared by coprecipitation, and gas chromatography was used to quantity the flavour compounds in the complexes. The ethyl butyrate-γ-CD complex had the highest inclusion ratio (12.20%) followed by the ethyl butyrate-β-CD, hexanal-β-CD and hexanal-γ-CD complexes (11.29, 4.41 and 3.33%, respectively). Release experiments were performed under different relative humidities (RH 93, 75 and 52%) and temperatures (4 and 25 °C). The flavour release behaviours of the complexes were described by the Avrami equation. The rate of flavour release was enhanced with both increasing temperature and RH, although the effect of RH was stronger. Physicochemical characterisation using FT-IR, XRD, DSC and SEM analyses demonstrated that crystalline complexes were formed. Both β-CD and γ-CD were able to encapsulate ethyl butyrate and hexanal, and lower RH and temperature were more suitable for the storage of these complexes.

Topics: beta-Cyclodextrins; Butyrates; Drug Compounding; Flavoring Agents; Food Industry; Food Preservation; gamma-Cyclodextrins; Hexobarbital; Humidity; Kinetics; Temperature

Supramolecular and bio-supramolecular host assisted pKa shift of biologically relevant acidic guests, warfarin and coumarin 343, has been monitored using both steady-state and time resolved fluorescence spectroscopy. The anion receptors present in sub-domain IIA of human serum albumin (HSA) stabilize the anionic form of the guest and thereby shift pKa towards acidic range. On the other hand, the preferential binding of the neutral form of guests in the non-polar hydrophobic cavity of β-cyclodextrin results in up-shifted pKa. This shifting of pKa of drugs like warfarin, etc., whose therapeutic activity depends on the position of the acid-base equilibrium in human system, is of great importance in pharmacokinetics. The release of the active form of such drugs from macrocyclic carrier and subsequent distribution through the carrier protein should depend on the modulation of the overall pKa window brought about by the encapsulation in these hosts. Present work also suggests that properly optimized encapsulation in appropriate receptor pocket can enhance the bioavailability of drugs. This work also opens up the possibility to use HSA as encapsulator, instead of traditional cyclodextrins or other polymeric hosts, since such system may overcome toxicity as well as biocompatibility issues.

Topics: beta-Cyclodextrins; Coumarins; gamma-Cyclodextrins; Humans; Hydrogen-Ion Concentration; Protein Structure, Tertiary; Serum Albumin; Warfarin

The gas chromatographic separation of enantiomers of 2-Br carboxylic acid derivatives was studied on four different 6-TBDMS-2,3-di-O-alkyl- β- and -γ-CD stationary phases. The differences in thermodynamic data {ΔH and -ΔS} for the 15 structurally related racemates were evaluated. The influence of structure differences in the alkyl substituents covalently attached to the stereogenic carbon atom, as well as in the ester group of the homologous analytes, and the selectivity of modified β- and γ- cyclodextrin derivatives was studied in detail. The cyclodextrin cavity size, as well as elongation of alkyl substituents in positions 2 and 3 of 6-TBDMS-β-CD, also affected their selectivity. The quality of enantiomeric separations is influenced mainly by alkyl chains of the ester group of the molecule and this appears to be independent of the CD stationary phase used. In some cases the separations occur as the result of external adsorption rather than inclusion complexations with the chiral selector. It was found that the temperature dependencies of the selectivity factor were nonlinear.

Topics: beta-Cyclodextrins; Bromine; Carboxylic Acids; Chromatography, Gas; Esters; gamma-Cyclodextrins; Siloxanes; Stereoisomerism; Styrenes; Thermodynamics

A novel ciprofloxacin loaded chitosan nanoparticle-based coating onto titanium substrates has been developed and characterized to obtain an orthopaedic implant surface able to in situ release the antibiotic for the prevention of post-operative infections. Ciprofloxacin loaded chitosan nanoparticles were obtained using the combination of sulfobutyl ether-beta-cyclodextrin and gamma-cyclodextrin. The resulting nanoparticulate system was characterized by TEM, HPLC and XPS. Particle size was in the range 426-552 nm and zeta potential values were around +30 mV. This antibacterial coating was able to in vitro inhibit two nosocomial Staphylococcus aureus strains growth, with a reduction of about 20 times compared to controls. No impairment in MG63 osteoblast-like cells viability, adhesion and gene expression were detected at 48 h, 7 and 14 days of culture. Overall, the investigated coating represents a promising candidate for the development of a new antibiotic carrier for titanium implants.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Cell Line; Chitosan; Ciprofloxacin; Coated Materials, Biocompatible; gamma-Cyclodextrins; Humans; Nanoparticles; Prostheses and Implants; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Titanium

A diradical-platinum(II) complex was able to recognize the subtle difference in cavity size between β- and γ-cyclodextrin with on-off switching of intense near-infrared absorption. This provides a new probe for identifying the size of hydrophobic cavities, which has been successfully applied here to differentiate human serum albumin from α-chymotrypsin.

Topics: Aminobenzoates; beta-Cyclodextrins; Chymotrypsin; Coordination Complexes; gamma-Cyclodextrins; Humans; Hydrophobic and Hydrophilic Interactions; Nuclear Magnetic Resonance, Biomolecular; Platinum; Serum Albumin; Spectrophotometry

Surface modified electrospun polyester (PET) nanofibers with cyclodextrin polymer (CDP) were produced (PET/CDP). CDP formation onto electrospun PET nanofibers was achieved by polymerization between citric acid (CTR, crosslinking agent) and cyclodextrin (CD). Three different types of native CD (α-CD, β-CD and γ-CD) were used to form CDP. Water-insoluble crosslinked CDP coating was permanently adhered onto the PET nanofibers. SEM imaging indicated that the nanofibrous structure of PET mats was preserved after CDP surface modification process. PET/CDP nanofibers have shown rougher/irregular surface and larger fiber diameter when compared to untreated PET nanofibers. The surface analyses of PET/CDP nanofibers by XPS elucidated that CDP was present on the fiber surface. DMA analyses revealed the enhanced mechanical properties for PET/CDP where PET/CDP nanofibers have shown higher storage modulus and higher glass transition temperature compared to untreated PET nanofibers. The surface area of the PET/CDP nanofibers investigated by BET measurements showed slight decrease due to the presence of CDP coating compared to pristine PET nanofibers. Yet, it was observed that PET/CDP nanofibers were more efficient for the removal of phenanthrene as a model polycyclic aromatic hydrocarbon (PAH) from aqueous solution when compared to pristine PET nanofibers. Our findings suggested that PET/CDP nanofibers can be a very good candidate as a filter material for water purification and waste treatment owing to their very large surface area as well as inclusion complexation capability of surface associated CDP.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cellulose; Cyclodextrins; gamma-Cyclodextrins; Nanofibers; Phenanthrenes; Polyesters; Surface Properties; Water Pollutants, Chemical; Water Purification

A polypseudorotaxane (PPR) comprising γ-cyclodextrin (γ-CD) as host molecules and poly(N-isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self-assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size-selectivity toward self-assembly with α-, β-, and γ-CDs. It can fit into the cavity of γ-CD to give rise to a PPR, but cannot pass through α-CD and β-CD under the same conditions. The ratio of the number of γ-CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by (1) H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ-CD molecule. This finding opens new avenues to PPR-based supramolecular polymers to be used as solid, stimuli-responsive materials.

Topics: Acrylamides; Acrylic Resins; beta-Cyclodextrins; gamma-Cyclodextrins; Molecular Structure; Polymerization; Polymers; Rotaxanes

Supramolecular host-guest interactions of oxazine-1 dye with β- and γ-cyclodextrins (βCD and γCD, respectively) have been investigated in neutral aqueous solution (pH ∼ 7) at ambient temperature (∼25 °C) following absorption, fluorescence, and circular dichroism measurements. The dye forms inclusion complexes with both CDs, causing significant changes in its photophysical properties. Whereas fluorescence titration data for lower dye concentrations fit well with 1:1 stoichiometric complexes, the time-resolved fluorescence results indicate formation of a small extent of 1:2 (dye-host) complexes as well, especially at higher CD concentrations. The moderate range of the binding constant values for the present systems indicates the weaker hydrophobic interaction as responsible for the inclusion complex formation in these systems. It has also been observed that γCD facilitates dimerization of the dye, prominently indicated at the higher dye concentrations. On the contrary, βCD always assists deaggregation of the dye, even at very high dye concentrations. Time-resolved fluorescence anisotropy results qualitatively support the inclusion complex formation in the present systems. Results from quantum chemical calculations also nicely corroborate with the inferences drawn from photophysical studies. Observed results demonstrate that the size compatibility of the guest and the host cavity mainly determines the host-guest interaction in the present systems, much similar to the substrate-catalyst binding in many biological systems.

Topics: beta-Cyclodextrins; Coloring Agents; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Macromolecular Substances; Molecular Structure; Oxazines; Photochemical Processes; Quantum Theory; Temperature

Solid-contact sensors for the selective screening of sulfadiazine (SDZ) in aquaculture waters are reported. Sensor surfaces were made from PVC membranes doped with tetraphenylporphyrin-manganese(III) chloride, α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin ionophores that were dispersed in plasticizer. Some membranes also presented a positive or a negatively charged additive. Phorphyrin-based sensors relied on a charged carrier mechanism. They exhibited a near-Nernstian response with slopes of 52 mV decade(-1) and detection limits of 3.91×10(-5) mol L(-1). The addition of cationic lipophilic compounds to the membrane originated Nernstian behaviours, with slopes ranging 59.7-62.0 mV decade(-1) and wider linear ranges. Cyclodextrin-based sensors acted as neutral carriers. In general, sensors with positively charged additives showed an improved potentiometric performance when compared to those without additive. Some SDZ selective membranes displayed higher slopes and extended linear concentration ranges with an increasing amount of additive (always <100% ionophore). The sensors were independent from the pH of test solutions within 2-7. The sensors displayed fast response, always <15s. In general, a good discriminating ability was found in real sample environment. The sensors were successfully applied to the fast screening of SDZ in real waters samples from aquaculture fish farms. The method offered the advantages of simplicity, accuracy, and automation feasibility. The sensing membrane may contribute to the development of small devices allowing in locus measurements of sulfadiazine or parent-drugs.

Topics: alpha-Cyclodextrins; Animals; Aquaculture; beta-Cyclodextrins; Biosensing Techniques; Fishes; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Ionophores; Membranes, Artificial; Metalloporphyrins; Molecular Structure; Potentiometry; Quaternary Ammonium Compounds; Reproducibility of Results; Sulfadiazine; Water Pollutants, Chemical

An extensive dynamic and structural characterization of the supramolecular complexes that can be formed by mixing α-, β-, and γ-cyclodextrin (CD) with sodium dodecyl sulfate (SDS) in water at 283, 298, and 323 K was performed by means of computational molecular dynamics simulations. For each CD at the three temperatures, seven different initial conformations were used, generating a total of 63 trajectories. The observed stoichiometries, intermolecular distances, and relative orientation of the individual molecules in the complexes, as well as the most important interactions which contribute to their stability and the role of the solvent water molecules were studied in detail, revealing clear differences and similarities between the three CDs. Earlier reported findings in the inclusion complexes field are also discussed in the context of the present results. For any of the three native cyclodextrins, the CD(2)SDS(1) species in the head-to-head conformation appears to be a promising building block for nanotubular aggregates both in the bulk and at the solution/air interface, as earlier suggested for the case of α-CD. Moreover, the observed noninclusion arrangements involving β-CD are proposed as the seed for the premicellar (β-CD)-induced aggregation of SDS described in the literature.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; gamma-Cyclodextrins; Molecular Dynamics Simulation; Sodium; Sodium Dodecyl Sulfate; Temperature; Time Factors

Three types of cyclodextrin nanosponges were synthetized cross-linking α, β or γ cyclodextrin with carbonyldiimidazole as cross-linker. Nanosponges are solid nanoparticles previously used as drug carriers. In this studies cyclodextrin nanosponges were developed as oxygen delivery system. For this purpose the three types of nanosponges suspended in water were saturated with oxygen and in vitro characterized. The nanosponge safety was tested on Vero cells. Their ability to release oxygen in the presence and in the absence of ultrasound (US) was determined over time. Oxygen permeation through a silicone membrane was obtained using a β-cyclodextrin nanosponge/hydrogel combination system. Nanosponge formulations might be potential gas delivery systems showing the ability to store and to release oxygen slowly over time.

Topics: alpha-Cyclodextrins; Animals; beta-Cyclodextrins; Chlorocebus aethiops; Cross-Linking Reagents; Drug Carriers; gamma-Cyclodextrins; Imidazoles; Nanoparticles; Oxygen; Permeability; Time Factors; Ultrasonography; Vero Cells

Ginseng is one of the most popular functional ingredients found in energy drink formulations. Although ginseng is known for its health benefits, ginseng is also notorious for imparting a bitter taste. Incorporating ginseng into beverages without the bitterness, while still maintaining its health benefits, is necessary for developing an acceptable product. Thus, the objectives of this study were to (1) identify effective treatments for minimizing the bitterness of ginseng in water base and model energy drink base solutions and (2) determine the sensory effects of incorporating different treatment levels to minimize the bitterness of ginseng. A series of pilot studies investigating bitterness reducing treatments were conducted, which included: congruent flavor addition, bitterness blocking agent incorporation, enzymatic modification, ingredient interaction, and complexation. Based on the results of a series of pilot studies, γ-cyclodextrin (γ-CD) and β-cyclodextrin (β-CD) complexation agents were identified as having the most potential. Effectiveness of the γ-CDs, β-CDs, and combinations of γ- and β-CDs were tested in 100 mL water and in 100 mL model energy drink base solutions containing 0.052 g 80% ginsenosides panax ginseng, using descriptive sensory analysis. Twelve trained panelists evaluated 42 solution treatments (3 treatments × 7 levels × 2 bases) for bitter attributes with and without nose clips. Overall, the most effective treatments were 0.09 g γ-CDs in 100 mL of solution and 1 g β-CDs in 100 mL solution, which both reduced the bitterness intensity of the solutions by half. Incorporation of these levels of CDs in water and model energy drink base solutions containing ginseng will aid in the development of functional beverages that are more acceptable to a wider range of consumers.

Topics: Adolescent; Adult; beta-Cyclodextrins; Beverages; Female; Flavoring Agents; Food, Formulated; gamma-Cyclodextrins; Ginsenosides; Humans; Male; Middle Aged; Osmolar Concentration; Panax; Pilot Projects; Plant Roots; Sensation; Taste; United States; Young Adult

Emulsions consisting of n-alkane/water using alpha, beta, and gamma-cyclodextrin (alpha, beta, and gamma-CD) as an emulsifier were prepared and characterized by means of several physicochemical techniques. A phase diagram of the n-alkane/CD/water system showed that an oil in water (O/W) emulsion can be prepared from a mixture of the appropriate composition. The dissolved n-alkane/CD complexes formed at low CD concentrations showed surface-activity, but emulsions could not be prepared from these complexes. On the other hand, the precipitated complexes formed at high CD concentrations when adsorbed to the oil/water interface, and served as an emulsifier for formation of emulsions. These results showed that the emulsions formed were of the Pickering emulsion. In addition emulsion formation was governed by the wettability and the surface free energy of the precipitated complexes.

Topics: Adsorption; Alkanes; alpha-Cyclodextrins; beta-Cyclodextrins; Chemistry; Emulsions; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Oils; Plant Oils; Salts; Surface Properties; Temperature; Water

Cyclodextrin (CD) complexation procedures are relatively simple processes, but these techniques often require very specific conditions for each individual guest molecule. Variations of the coprecipitation from aqueous solution technique were optimized for the CD complexation of the natural antioxidants alpha-tocopherol and quercetin. Solid inclusion complex products of alpha-tocopherol/beta-CD and quercetin/gamma-CD had molar ratios of 1.7:1, which were equivalent to 18.1% (w/w) alpha-tocopherol and 13.0% (w/w) quercetin. The molar reactant ratios of CD/antioxidant were optimized at 8:1 to improve the yield of complexation. The product yields of alpha-tocopherol/beta-CD and quercetin/gamma-CD complexes from their individual reactants were calculated as 24 and 21% (w/w), respectively. ATR/FT-IR, 13C CP/MAS NMR, TGA, and DSC provided evidence of antioxidant interaction with CD at the molecular level, which indicated true CD inclusion complexation in the solid state. Natural antioxidant/CD inclusion complexes may serve as novel additives in controlled-release active packaging to extend the oxidative stability of foods.

Topics: alpha-Tocopherol; Antioxidants; beta-Cyclodextrins; Chemical Precipitation; Cyclodextrins; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Quercetin; Spectroscopy, Fourier Transform Infrared; Thermodynamics

In recent years cyclodextrins (CDs) have been acknowledged by the pharmaceutical industry as very useful enabling excipients for solubilization and stabilization of drugs in aqueous formulations. Their effect is however strongly influenced by other commonly used excipients. The purpose of this investigation was to examine the effects of excipients and drug combinations on the effects of CD solubilization of drugs and drug availability. The model drug was dexamethasone, the competing drugs tested were hydrocortisone, indomethacin and amphotericin B, and the sample CDs were gamma-cyclodextrin (gammaCD) and 2-hydroxypropyl-gamma-cyclodextrin (HPgammaCD). Benzalkonium chloride and hydroxypropyl methylcellulose enhance the solubilizing effect of the CDs whereas in general EDTA decreased the effect. The effect of second drug present in the aqueous formulation did depend on the affinity of that drug for the CD. Drugs which readily formed complexes with the CDs (e.g. hydrocortisone) decreased their ability to solubilize dexamethasone. Drugs that have little affinity for CDs (e.g. amphotericin B) did in some cases improve the CD solubilization of dexamethasone. Flux diagrams obtained through semi-permeable cellophane membrane indicated that drug/CD complexes self-assemble to form aggregates, especially at CD concentrations above 5% (w/v). This aggregate formation was affected by the excipients and did influence drug availability from the formulations.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Amphotericin B; Benzalkonium Compounds; beta-Cyclodextrins; Chemistry, Pharmaceutical; Dexamethasone; Edetic Acid; Excipients; gamma-Cyclodextrins; Hydrocortisone; Hypromellose Derivatives; Indomethacin; Methylcellulose; Solubility

Water-soluble supramolecular inclusion complexes of alpha-, beta-, and gamma-cyclodextrin-bicapped C60 (CD/C60) have been investigated for their photoinduced DNA cleavage activities, with the aim to assess the potential health risks of this class of compounds and to understand the effect of host cyclodextrins having different cavity dimensions. Factors such as incubation temperature, irradiation time, and concentration of NADH or CDs/ C60 supramolecular inclusion complexes have been examined. The results show that alpha-, beta-, and gamma-CDs/C60 are all able to cleave double-stranded DNA under visible light irradiation in the presence of NADH. However, a difference in the photoinduced DNA cleavage efficiency is observed, where the cleavage efficiency increases in the order of alpha-, beta-, and gamma-CD/C60. The difference is attributed to the different aggregation behavior of the inclusion complexes in aqueous solution, which is correlated to the cavity dimension of the host cyclodextrin molecules.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; DNA; DNA Damage; Environmental Exposure; Environmental Monitoring; Fullerenes; gamma-Cyclodextrins; Humans; Light; Macromolecular Substances; NAD; Risk; Temperature

The main focus of this study was to explore the capability of native alpha-cyclodextrin, beta-cyclodextrin and gamma-cyclodextrin and their hydroxypropyl derivatives for host-guest interaction with 7,8-dimethoxyflavone, selected steroids (estetrol, estriol, estradiol, estrone, testosterone, cortisone, hydrocortisone, progesterone and 17alpha-hydroxyprogesterone) and polycyclic aromatic hydrocarbons (toluene, naphthalene, 1,8-dimethylnaphthalene, 1-acenaphthenol, acenaphthylene and acenaphthene) under reversed-phase liquid-chromatography conditions. The study revealed that native cyclodextrins interact more efficiently with the analytes investigated than do their hydroxypropyl counterparts. In the low-temperature region, enormously high ratios were observed for polycyclic aromatic hydrocarbons, particularly 1,8-dimethylnaphthalene, acenaphthene and acenaphthylene chromatographed on a beta-cyclodextrin-modified mobile phase. In such a case, the retention times of the polycyclic aromatic hydrocarbons were strongly reduced (e.g. from 127 to 1.2 min for 1,8-dimethylnaphthalene) and were close to the hold-up time of the high-performance liquid chromatography (HPLC) system (0.7 min). Moreover, chiral separation of 1-acenaphthenol optical isomers was observed and the elution order of the enantiomers was determined. Within the steroids group, strong interaction was observed for estradiol and testosterone. The results of cluster analysis indicate that beta-cyclodextrin as well as gamma-cyclodextrin and its hydroxypropyl derivative can be most effective mobile-phase additives under reversed-phase HPLC conditions for 3D-shape-recognition-driven separation, performed at subambient and elevated temperatures, respectively.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; alpha-Cyclodextrins; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Circular Dichroism; gamma-Cyclodextrins; Models, Molecular; Molecular Structure; Molecular Weight; Oligosaccharides; Organic Chemicals; Polycyclic Aromatic Hydrocarbons; Steroids; Temperature

A systematic study of the host-guest complexation by alpha-, beta-, and gamma-cyclodextrin (CD) in either the free state or as substituents of poly(acrylic acid) (PAA) with the hydrophobic n-octadecyl groups, C18, substituted onto PAA (HMPAA) and its effect on polymer aggregation and network formation is reported. Free alpha-CD, beta-CD, and gamma-CD mask hydrophobic associations between the C18 substituent of HMPAA in aqueous solution and form host-guest complexes with a 1:1 or CD:C18 substituent stoichiometry at 0.5 wt % polymer concentration. For alpha-CD this host-guest stoichiometry changes to 2:1 or 2alpha-CD:C18 at > or =1 wt % polymer concentrations but not for beta-CD and gamma-CD. Shear-thickening occurs when gamma-CD complexes C18 HMPAA substituents. Upon addition of sodium dodecyl sulfate, SDS (SDS:CD = 1:1), the hydrophobic associations between C18 diminished by alpha-CD masking were fully restored, were only partly restored in the case of beta-CD, and not restored for gamma-CD. When alpha- and beta-CD substituted PAA (alpha-CDPAA and beta-CDPAA) were mixed with HMPAA polymer, networks formed. As for free beta-CD, the beta-CD substituents of beta-CDPAA also formed 1:1 or beta-CD:C18 stoichiometry host-guest complexes with the C18 substituents of HMPAA. The alpha-CD substituents of alpha-CDPAA also formed 1:1 or alpha-CD:C18 stoichiometry host-guest complexes with some indication of the formation of 2:1 or 2alpha-CD:C18 stoichiometry host-guest complexes at polymer concentrations > or =1 wt %. The polymer networks formed by beta-CDPAA with HMPAA are less viscous than those formed by alpha-CDPAA, for which shear-thickening occurs at polymer concentrations > or =2 wt %. It is evident that the difference in CD annular size and its match with the C18 of HMPAA control the diversity of the interactions of alpha-CD, beta-CD, gamma-CD, alpha-CDPAA, and beta-CDPAA with HMPAA.

Topics: Acrylic Resins; alpha-Cyclodextrins; beta-Cyclodextrins; gamma-Cyclodextrins; Molecular Structure; Viscosity

A continuous external shaking for 2.5 days of a mixture composed of alpha-cyclodextrin (6%), soybean oil (19.6%) and water (74.4%) resulted in a calibrated lipid carrier namely bead with a high fabrication yield. The purpose of this work was to explore the possibility to substitute alpha-cyclodextrin by other natural cyclodextrins, i.e. beta- and gamma-cyclodextrin and then soybean oil by mineral (Primol) 352 and Marcol 82) or synthetic (Silicon 200) fluid 10, 50 or 100cSt) oils. Beads can be successfully prepared using Marcol 82 with alpha-cyclodextrin and Silicon 50 or 100cSt with gamma-cyclodextrin. The area inside oil/cyclodextrin/water ternary diagram corresponding to bead occurrence was superior for the Marcol 82/alpha-cyclodextrin couple compared to that observed with soybean oil/alpha-cyclodextrin couple. Only a few ratios of Silicon 50 and 100cSt/gamma-cyclodextrin/water led to beads. The combinations which did not induce bead occurrence gave either emulsions, two non-miscible liquids or a solid mixture. Whatever the materials used, beads exhibited similarities: presence of a crystalline organisation and viscoelastic properties. Manufacturing process of paraffin- and silicon-based beads need further optimisation to increase fabrication yield and later on, to take advantages from the high stability of both oils for the formulation of drugs with beads.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chemistry, Pharmaceutical; Crystallization; Dosage Forms; Drug Carriers; Drug Stability; Elasticity; Emulsions; gamma-Cyclodextrins; Oils; Particle Size; Phase Transition; Rheology; Viscosity

A novel enzyme, RA.04, belonging to the alpha-amylase family was obtained after expression of metagenomic DNA from rumen fluid (Ferrer et al.: Environ. Microbiol. 2005, 7, 1996-2010). The purified RA.04 has a tetrameric structure (280 kDa) and exhibited maximum activity (5000 U/mg protein) at 70 degrees C and was active within an unusually broad pH range from 5.5 to 9.0. It maintained 80% activity at pH 5.0 and 9.5 and 75 degrees C. The enzyme hydrolyzed alpha-D-(1,4) bonds 13-fold faster than alpha-D-(1,6) bonds to yield maltose and glucose as the main products, and it exhibited transglycosylation activity. Its preferred substrates, in the descending order, were maltooligosaccharides (C3-C7), cyclomaltoheptaose (beta-CD), cyclomaltohexaose (alpha-CD), cyclomaltooctaose (gamma-CD), soluble starch, amylose, pullulan and amylopectin. The biochemical properties and amino acid sequence alignments suggested that this enzyme is a cyclomaltodextrinase. However, despite the similarity in the catalytic module (with Glu359 and Asp331 being the catalytic nucleophile and substrate-binding residues, respectively), the enzyme bears a shorter N-terminal domain that may keep the active site more accessible for both starch and pullulan, compared to the other known CDases. Moreover, RA.04 lacks the well-conserved N-terminal Trp responsible for the substrate preference typical of CDases/MAases/PNases, suggesting a new residue is implicated in the preference for cyclic maltooligosaccharides. This study has demonstrated the usefulness of a metagenomic approach to gain novel debranching enzymes, important for the bread/food industries, from microbial environments with a high rate of plant polymer turnover, exemplified by the cow rumen.

Topics: alpha-Cyclodextrins; Amylopectin; Amylose; Animals; Bacterial Proteins; beta-Cyclodextrins; Binding Sites; Catalysis; Cattle; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; gamma-Cyclodextrins; Glucans; Glycoside Hydrolases; Hydrogen-Ion Concentration; Maltose; Oligosaccharides; Rumen; Starch; Substrate Specificity; Temperature

The objective of this work was to develop tablet formulations of nimesulide-beta-cyclodextrin (NI-beta-CD) and meloxicam-gamma-cyclodextrin (ME-gamma-CD) binary systems. In the case of nimesulide, 3 types of binary systems--physical mixtures, kneaded systems, and coevaporated systems--were studied. In the case of meloxicam, 2 types of binary systems--physical mixtures and kneaded systems--were investigated. Both drug-CD binary systems were prepared at 1:1 and 1:2 molar ratio (1:1M and 1:2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40 degrees C +/- 2 degrees C and 75% relative humidity.

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Drug Stability; gamma-Cyclodextrins; Meloxicam; Solubility; Sulfonamides; Tablets; Thiazines; Thiazoles

Hydrogen-bonded interactions in alpha-, beta-, and gamma-CD conformers are investigated from the molecular electron density topography and chemical shift in the nuclear magnetic resonance (NMR) spectra calculated by using the Gauge Invariant Atomic Orbital (GIAO) method within the framework of density functional theory. For the lowest-energy CD conformers in the gas phase, the O3-H...O2' hydrogen-bonding interactions are present. Calculated 1H NMR chemical shifts (delta H) correlate well with the hydrogen-bond distance as well as electron density at the bond critical point in the molecular electron density (MED) topography. The conformers of beta- and gamma-CD comprised of relatively strong secondary hydroxyl interactions are stabilized by solvation from polar solvents.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Carbohydrate Conformation; Computer Simulation; gamma-Cyclodextrins; Glucose; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Models, Molecular; Protons; Solvents; Static Electricity; Thermodynamics

Here, we report a study on the complexation behavior of carotenoids with cyclodextrins (CDs) using solubility experiments and molecular-modelling methods. Carotenoids are an important group of naturally occurring dyes found in vegetables and fruits. Their antioxidant property has initiated investigations on their possible use as drugs. However, carotenoids are lipophilic molecules with very little inherent aqueous solubility. Cyclodextrin complexation has been widely used in order to increase the potential applications of hydrophobic compounds. Thus, the aim of our investigation was to design carotenoids with enhanced water solubility by cyclodextrin complexation. Molecular modelling of carotenoid-cyclodextrin complexes with a 1 : 1 stoichiometry successfully explained the experimentally observed capability of beta-cyclodextrins (beta-CDs) to form complexes with carotenoids as opposed to alpha-cyclodextrins (alpha-CDs) and gamma-cyclodextrins (gamma-CDs). Furthermore, molecular-dynamics calculations revealed that the aggregation properties of CD derivatives significantly influence their complexation behavior. Our docking calculations showed that RAMEB (random methylated beta-CD) is the beta-CD derivative that possesses the lowest tendency to aggregate. Solubility experiments yielded the same results, namely, RAMEB complexes possess the best water solubility. Our results showed that complexation of a ligand not buried inside of the CD cavity is dependent on two factors: i) the geometry of the inclusion part of the complex; ii) the self-aggregation property of the CD itself. The lower affinity the CDs possess for self-aggregation, the more likely are they involved in interactions with carotenoids. These results suggest that self-aggregation of CDs should be considered as an important parameter determining complexation in general.

Topics: Antioxidants; beta-Cyclodextrins; Carotenoids; Computer Simulation; Cyclodextrins; gamma-Cyclodextrins; Humans; Macromolecular Substances; Models, Chemical; Models, Molecular; Solubility; Thermodynamics; Vitamin A; Water

Powdery encapsulation of shiitake flavors, extracted from dried shiitake, was investigated by spray drying. Flavor retention increased with an increase in drying air temperature and solid content, and decreased with an increase in dextrose equivalents of maltodextrin. A heat-treatment of the extract liquid made the lenthionine concentration increase, but did not influence the concentrations of the other flavors. The formation of lenthionine with heat-treatment could be described by the consecutive unimolecular-type first order reaction. Lenthionine content in a spray-dried powder prepared with the heated extracted liquid significantly increased. alpha-Cyclodextrin was the most suitable encapsulant of alpha-, beta-, and gamma-cyclodextrins to prepare the spray-dried powder, including lenthionine. The flavor retentions were markedly increased by using of alpha-cyclodextrin and maltodextrin in combination as an encapsulant.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Capsules; Cyclodextrins; Food Technology; gamma-Cyclodextrins; Hot Temperature; Polysaccharides; Powders; Shiitake Mushrooms; Taste; Temperature; Thiepins

The host-guest interaction between the steroid antibiotics sodium fusidate and potassium helvolate as guests and the hosts beta- and gamma-cyclodextrin was studied by 13C and 1H NMR techniques. The analysis of chemical shifts of individual nuclei leads to inconsistent values of the association constants and fails generally in the case of mixtures of 1:1 and 1:2 stoichiometries. The problem of parameter correlation is identified and the global analysis of two or more nuclei is proposed as a very effective method for the detection of complexes of higher stoichiometries and for the precise determination of the involved association constants. A matrix formulation of global analysis and the determination of confidence intervals is described. An analytical solution of the cubic equation, necessary for the description of higher order complexes, is presented in detail and its use together with commercial fitting software is compared with dedicated implementations. gamma-Cyclodextrin forms with both studied steroids, sodium fusidate and potassium helvolate, 1:1 complexes with high values of the association constants, K(1)=(60+/-24)x10(3)lmol(-1), and K(2)=(22+/-9)x10(3)lmol(-1), respectively. To the contrary, beta-cyclodextrin forms 1:1 and 1:2 (guest:host) complexes with both steroids, with moderate K(1) and low K(2) values (K(1)=(0.74+/-0.13)x10(3)lmol(-1), K(2)=(0.210+/-0.075)x10(3)lmol(-1)), and (K(1)=(2.42+/-0.87)x10(3)lmol(-1), K(2)=(0.06+/-0.09)x10(3)lmol(-1)), respectively.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Carbon Isotopes; Cyclodextrins; Drug Delivery Systems; Fusidic Acid; gamma-Cyclodextrins; Models, Chemical; Models, Theoretical; Nuclear Magnetic Resonance, Biomolecular; Protons

The complexation of two steroid antibiotics of the fusidane family, sodium fusidate and potassium helvolate, by beta-CD and gamma-CD has been studied by using 1D and 2D-NMR techniques. Both guests form 1:1 complexes with gamma-CD and 1:2 (guest:cyclodextrin) complexes with beta-CD. Thus, both antibiotics behave as monotopic and ditopic guests when they are complexed by gamma-CD and beta-CD, respectively. Both steroids enter into the cavity of the gamma-CD by the side chain, reaching the central region of the steroid (rings C and D), whereas the A and B (partially) rings remain outside. For beta-CD complexes, ROESY spectra show a remarkable absence of interactions of the protons of the C and D rings, whereas clear interactions corresponding to the side chain, and A and B rings are observed. The obtained equilibrium constants (see previous paper) are discussed in terms of the structures proposed for the complexes. NMR spectra of sodium fusidate are revised, and a full assignment of the 1H and 13C NMR spectra is presented for potassium helvolate.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Binding Sites; Cyclodextrins; Drug Delivery Systems; Fusidic Acid; gamma-Cyclodextrins; Models, Chemical; Models, Theoretical; Nuclear Magnetic Resonance, Biomolecular

The inclusion complexation behavior of chiral members of cinchona alkaloid with beta- and gamma-cyclodextrins (1 and 2) and 6,6(')-trimethylenediseleno-bridged bis(beta-cyclodextrin) (3) was assessed by means of fluorescence and 2D-NMR spectroscopy. The spectrofluorometric titrations have been performed in aqueous buffer solution (pH 7.20) at 25.0 degrees C to determine the stability constants of the inclusion complexation of 1-3 with guest molecules (i.e., cinchonine, cinchonidine, quinine, and quinidine) in order to quantitatively investigate the molecular selective binding ability. The stability constants of the resulting complexes of 2 with guest molecules are larger than that of 1. As a result of cooperative binding, the stability constants of inclusion complexation of dimeric beta-cyclodextrin 3 with cinchonidine and cinchonine are higher than that of parent 1 by factor of 4.5 and 2.4, respectively. These results are discussed from the viewpoint of the size-fit and geometric complementary relationship between the host and guest.

Topics: beta-Cyclodextrins; Binding Sites; Cinchona Alkaloids; Cyclodextrins; gamma-Cyclodextrins; Macromolecular Substances; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Organoselenium Compounds; Selenium; Sensitivity and Specificity; Spectrometry, Fluorescence; Stereoisomerism

This study systematically investigates the optimal conditions for analyzing the positional isomers of multi-charged naphthalenesulfonate compounds by cyclodextrin-mediated capillary electrophoresis (CE). Specifically, this work employs large-volume sample injection with the electrode polarity switching technique. The most effective separation and sample stacking conditions were 15 mM borate buffer with a mixture of beta- and gamma-cyclodextrin (concentration ratio 3:7 mM) at pH 9.2, and the sample hydrodynamic injection of up to 60 s at 3 p.s.i. (around 1.8 microl, and 1 p.s.i. = 6.9 kPa). Significantly selective and sensitive improvements were observed and a more than 100-fold enrichment was achieved (based on peak area). The reproducibility of migration time and quantitative results of stacking CE can be improved by using an internal standard. The quantitation limits of these naphthalenesulfonate isomers, based on a signal-to-noise ratio above 10, can be about 4 microg/l with UV detection. This method was successfully applied to determine the trace amount of naphthalenesulfonate isomers in a spiked drinking water sample.

Topics: beta-Cyclodextrins; Boric Acids; Buffers; Cyclodextrins; Electrophoresis, Capillary; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Microchemistry; Naphthalenesulfonates; Quality Control; Reproducibility of Results; Sensitivity and Specificity; Water; Water Pollutants

Camphor (CA) encapsulation in oil/water/oil multiple emulsions prepared with cyclodextrin disturbs the emulsifier potential of alpha- and beta-natural cyclodextrins (CD). It was suggested that the size and geometrical fit between the CD cavity and CA could induce CD/CA complex formation in place of emulsifier formation leading to perturbation of emulsion stability. The complexation between CA and alpha-, beta- or gamma-CD in solution in the presence of oil phase are confirmed by phase-solubility diagrams, circular dichroism and 1H NMR. Furthermore, in order to mimic the emulsion system, CD/CA/soybean oil ternary dispersions were prepared to observe the complexation behavior of alpha-, beta- or gamma-CD/CA by circular dichroism. X-ray diffraction on emulsion samples prepared with alpha- and beta-CD confirms that the precipitates observed in emulsions are probably composed of crystals of CD/CA complexes. A preliminary study of the interaction between drug and CD before the formulation seems indispensable to prevent the risk of incompatibility.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Camphor; Chemistry, Pharmaceutical; Circular Dichroism; Crystallization; Cyclodextrins; Drug Stability; Emulsions; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Molecular Weight; Solubility; Soybean Oil; Surface-Active Agents; Water; X-Ray Diffraction

A number of regulatory binding sites of glycogen phosphorylase (GP), such as the catalytic, the inhibitor, and the new allosteric sites are currently under investigation as targets for inhibition of hepatic glycogenolysis under high glucose concentrations; in some cases specific inhibitors are under evaluation in human clinical trials for therapeutic intervention in type 2 diabetes. In an attempt to investigate whether the storage site can be exploited as target for modulating hepatic glucose production, alpha-, beta-, and gamma-cyclodextrins were identified as moderate mixed-type competitive inhibitors of GPb (with respect to glycogen) with K(i) values of 47.1, 14.1, and 7.4 mM, respectively. To elucidate the structural basis of inhibition, we determined the structure of GPb complexed with beta- and gamma-cyclodextrins at 1.94 A and 2.3 A resolution, respectively. The structures of the two complexes reveal that the inhibitors can be accommodated in the glycogen storage site of T-state GPb with very little change of the tertiary structure and provide a basis for understanding their potency and subsite specificity. Structural comparisons of the two complexes with GPb in complex with either maltopentaose (G5) or maltoheptaose (G7) show that beta- and gamma-cyclodextrins bind in a mode analogous to the G5 and G7 binding with only some differences imposed by their cyclic conformations. It appears that the binding energy for stabilization of enzyme complexes derives from hydrogen bonding and van der Waals contacts to protein residues. The binding of alpha-cyclodextrin and octakis (2,3,6-tri-O-methyl)-gamma-cyclodextrin was also investigated, but none of them was bound in the crystal; moreover, the latter did not inhibit the phosphorylase reaction.

Topics: alpha-Cyclodextrins; Animals; beta-Cyclodextrins; Binding Sites; Circular Dichroism; Crystallography, X-Ray; Cyclodextrins; gamma-Cyclodextrins; Glucans; Glucose; Glycogen; Glycogen Phosphorylase, Muscle Form; Hydrogen Bonding; Kinetics; Models, Chemical; Oligosaccharides; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Rabbits

The present study was conducted to investigate the inclusion complexation of artemisinin (ART) with natural cyclodextrins (CyD), namely alpha-, beta-, and gamma-CyDs with the aim of improving its solubility and dissolution rate. Complex formation in aqueous solution and solid state was studied by solubility analysis, dissolution, and thermal analysis. Solubility diagrams indicated that the complexation of ART and the three CyDs occurred at a molar ratio of 1:1, and showed a remarkable increase in ART solubility. Moreover, the thermodynamic parameters calculated by using the van't Hoff equation revealed that the complexation process was associated with negative enthalpy of formation and occurred spontaneously. The complexation capability of CyDs with ART increased in the order of alpha- < gamma- < beta-CyDs and could be ascribed to the structural compatibility between the molecular size of ART and the diameter of the CyD cavities. Dissolution profiles of the three complexes demonstrated an increased rate and extent of dissolution compared with those of their respective physical mixtures and a commercial preparation. In solid-state analysis, using differential scanning calorimetry, the gamma-CyD was capable of complexing the highest percentage of ART, followed by beta- and alpha-CyDs. The respective estimated percentage of ART complexed by the CyDs were 85%, 40%, and 12%.

Topics: alpha-Cyclodextrins; Artemisinins; beta-Cyclodextrins; Cyclodextrins; Dose-Response Relationship, Drug; gamma-Cyclodextrins; Sesquiterpenes; Solubility

Natamycin is a broad spectrum antimycotic with very low water solubility, which is used to extend the shelf life of shredded cheese products. beta-Cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin (HP beta-CD), and gamma-cyclodextrin (gamma-CD) were found to form inclusion complexes with natamycin in aqueous solution. The increase in solubility of natamycin with added beta-CD was observed to be linear (type A(L) phase solubility diagram). The 1:1 stability constant of natamycin:beta-CD complex was estimated from its phase solubility diagram to be 1010 M(-1). The phase solubility diagrams of both gamma-CD and HP beta-CD exhibited negative deviation from linearity (type A(N) diagram) and, therefore, did not allow the estimation of binding constants. The water solubility of natamycin was increased 16-fold, 73-fold, and 152-fold with beta-CD, gamma-CD, and HP beta-CD, respectively. The natamycin:CD inclusion complexes resulted in in vitro antifungal activity nearly equivalent to that of natamycin in its free state.

Topics: Antifungal Agents; beta-Cyclodextrins; Cheese; Cyclodextrins; Food Preservation; gamma-Cyclodextrins; Hot Temperature; Natamycin; Solubility; Solutions; Spectrophotometry, Ultraviolet; Water

Aqueous solutions of natamycin and its beta-cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin, and gamma-cyclodextrin (gamma-CD) inclusion complexes were completely degraded after 24 h of exposure to 1000 lx fluorescent lighting at 4 degrees C. After 14 days of storage in darkness at 4 degrees C, 92.2% of natamycin remained in active form. The natamycin:beta-CD complex and natamycin:gamma-CD complex were significantly more stable (p < 0.05) than natamycin in its free state in aqueous solutions stored in darkness at 4 degrees C. Clear poly(ethylene terephthalate) packaging with a UV light absorber allowed 85.0% of natamycin to remain after 14 days of storage under 1000 lx fluorescent lighting at 4 degrees C. Natamycin:cyclodextrin complexes can be dissociated for analysis in methanol/water/acetic acid, 60:40:5, v/v/v. Natamycin and its complexes in dissociated form were quantified by reverse phase HPLC with detection by photodiode array at 304 nm.

Topics: Antifungal Agents; beta-Cyclodextrins; Cyclodextrins; Drug Stability; gamma-Cyclodextrins; Light; Methanol; Natamycin; Solutions; Water

To explore the use of cyclodextrins (CD) to form inclusion complexes with beta-lapachone (beta-lap) to overcome solubility and bioavailability problems previously noted with this drug.. Inclusion complexes between beta-lap and four cyclodextrins (alpha-, beta-, gamma-, and HPbeta-CD) in aqueous solution were investigated by phase solubility studies, fluorescence, and 1H-NMR spectroscopy. Biologic activity and bioavailability of beta-lap inclusion complexes were investigated by in vitro cytotoxicity studies with MCF-7 cells and by in vivo lethality studies with C57Blk/6 mice (18-20 g).. Phase solubility studies showed that beta-lap solubility increased in a linear fashion as a function of alpha-, beta-, or HPbeta-CD concentrations but not gamma-CD. Maximum solubility of beta-lap was achieved at 16.0 mg/ml or 66.0 mM with HPbeta-CD. Fluorescence and 1H-NMR spectroscopy proved the formation of 1:1 inclusion complexes between beta-CD and HPbeta-CD with beta-lap. Cytotoxicity assays with MCF-7 cells showed similar biologic activities of beta-lap in beta-CD or HPbeta-CD inclusion complexes (TD50 = 2.1 microM). Animal studies in mice showed that the LD50 value of beta-lap in an HPbeta-CD inclusion complex is between 50 and 60 mg/kg.. Complexation of beta-lap with HPbeta-CD offers a major improvement in drug solubility and bioavailability.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Adjuvants, Pharmaceutic; alpha-Cyclodextrins; Animals; beta-Cyclodextrins; Biological Availability; Cyclodextrins; gamma-Cyclodextrins; Humans; Injections, Intraperitoneal; Lethal Dose 50; Mice; Mice, Inbred C57BL; Naphthoquinones; Solubility; Tumor Cells, Cultured

Beta-cyclodextrin, which forms stable host-guest complexes with purine bases, induces the melting of RNA and DNA duplexes below their normal melting temperatures. Alpha-cyclodextrin, which does not form stable complexes, has no effect on either RNA or DNA. Gamma-cyclodextrin, which forms weaker complexes, has no effect on RNA and a smaller effect than beta-cyclodextrin on DNA. The rate of melting is kinetically first-order in duplex and, above about 20 mM beta-cyclodextrin, is independent of the beta-cyclodextrin concentration with a first-order rate constant, common to both RNA and DNA, of (3.5 +/- 0.5) x 10(-3) s(-1) at 61 degrees C (DNA) and at 50 degrees C (RNA). This is taken to be the rate constant for spontaneous "flipping out" of a base from within the duplex structure of the nucleic acids, the exposed base being rapidly trapped by beta-cyclodextrin. Like beta-cyclodextrin, nucleic acid methyltransferases bind the target base for methylation in a site that requires it to have flipped out of its normal position in the duplex. The spontaneous flip-out rate constant of around 10(-3) s(-1) is near the value of k(cat) for the methyltransferases (ca. 10(-3) to 10(-1) s(-1)). In principle, the enzymes, therefore, need effect little or no catalysis of the flipping-out reaction. Nevertheless, the flip-out rate in enzyme/DNA complexes is much faster. This observation suggests that the in vivo circumstances may differ from in vitro models or that factors other than a simple drive toward higher catalytic power have been influential in the evolution of these enzymes.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Physical; Cyclodextrins; DNA; gamma-Cyclodextrins; Kinetics; RNA; Spectrophotometry, Ultraviolet

Conjugated linoleic acid (CLA) inclusion complexes with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), and gamma-cyclodextrin (gamma-CD) (designated CLA/CDs inclusion complexes) were prepared to determine the mole ratio of CLA complexed with CDs and the oxidative stability of CLA in the CLA/CDs inclusion complexes. When measured by GC, (1)H NMR, and T(1) value analyses, 1 mole of CLA was complexed with 5 mol of alpha-CD, 4 mol of beta-CD, and 2 mol of gamma-CD. The oxidation of CLA induced at 35 degrees C for 80 h was completely prevented by the formation of CLA/CDs inclusion complexes.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chromatography, Gas; Cyclodextrins; Drug Stability; gamma-Cyclodextrins; Linoleic Acid; Magnetic Resonance Spectroscopy; Oxidation-Reduction

The effects of alpha-, beta- and gamma-cyclodextrins on the amylose and maltopentaose hydrolysis catalysed by porcine pancreatic alpha-amylase (PPA) were investigated. The results of the statistical analysis performed on the kinetic data using the general initial velocity equation of a one-substrate reaction in the presence of one inhibitor indicate that the type of inhibition involved depends on the substrate used: the inhibition of amylose hydrolysis by alpha-, beta- and gamma-cyclodextrin is of the competitive type, while the inhibition of maltopentaose hydrolysis is of the mixed noncompetitive type. Consistently, the Lineweaver-Burk plots intersect on the vertical axis when amylose is used as the substrate, while in the case of maltopentaose, the intersection occurs at a point located in the second quadrant. The inhibition of the hydrolysis therefore involves only one abortive complex, PPA-cyclodextrin, when amylose is used as the substrate, while two abortive complexes, PPA-cyclodextrin and PPA-maltopentaose-cyclodextrin, are involved with maltopentaose. The mixed noncompetitive inhibition thus shows the existence of one accessory binding site. In any case, only one molecule of inhibitor binds to PPA. In line with these findings, the difference spectra of PPA produced by alpha-, beta- and gamma-cyclodextrin indicate that binding occurs at a tryptophan and a tyrosine residue. The corresponding dissociation constants and the inhibition constants obtained using the kinetic approach are in the same range (1.2-7 mM). The results obtained here on the inhibition of maltopentaose hydrolysis by cyclodextrin are similar to those previously obtained with acarbose as the inhibitor [Alkazaz, M., Desseaux, V., Marchis-Mouren, G., Prodanov, E. & Santimone, M. (1998) Eur. J. Biochem. 252, 100-107], but differ from those obtained with amylose as the substrate and acarbose as inhibitor [Alkazaz, M., Desseaux, V., Marchis-Mouren, G., Payan, F., Forest, E. & Santimone, M. (1996) Eur. J. Biochem. 241, 787-796]. It is concluded that the hydrolysis of both long and short chain substrates requires at least one secondary binding site, including a tryptophan residue.

Topics: alpha-Amylases; alpha-Cyclodextrins; Amylose; Animals; beta-Cyclodextrins; Binding Sites; Binding, Competitive; Cyclodextrins; gamma-Cyclodextrins; Hydrolysis; Kinetics; Models, Chemical; Oligosaccharides; Pancreas; Spectrophotometry; Swine; Tryptophan

A new capillary electrophoretic method for trace analysis of gamma-cyclodextrin, gamma-CD, in a sample of beta-CD has been developed, building on our recent work in which the tetraphenylborate ion, Ph4B-, was found to bind to gamma-CD three orders of magnitude more strongly than to beta-CD. The method involves measurement of the change of net electrophoretic mobility of Ph4B- and its CD complexes in a background electrolyte containing a fixed concentration of beta-CD. Good linearity was found between 1/deltamu and 1/Cgamma where deltamu is the difference in the mobility of Ph4B- in the beta-CD solution at a given and at zero concentration of gamma-CD, and Cgamma the gamma-CD concentration. The limit of detection for gamma-CD in a beta-CD sample was found to be 0.020% (w/w), and high precision and accuracy were obtained.

Topics: beta-Cyclodextrins; Calibration; Cyclodextrins; Electrophoresis, Capillary; gamma-Cyclodextrins; Reproducibility of Results; Sensitivity and Specificity

The use of capillary zone electrophoresis (CZE) for the separation of a group of 33 2,4-dinitrophenyl labeled amino acids (DNP-AA), including DNP-AA racemates, DNP-L-AA enantiomers and achiral DNP-AAs, was investigated. Alpha-, beta- and gamma-cyclodextrins (CDs) and their derivatives (hydroxypropyl derivatives of alpha-, beta- and gamma-CDs, polymeric beta-CD and 6A-methylamino-beta-cyclodextrin (MA-beta-CD)) served as complexing agents and chiral selectors in this investigation. Although native alpha- and gamma-CDs and their derivatives influenced the effective mobilities of the studied DNP-AAs in different ways, they generally failed to resolve enantiomers of the individual DNP-AAs. On the other hand, beta-CD and all of its derivatives were found to be effective in this respect. Of these, the best results were achieved with a positively charged MA-beta-CD and this chiral selector resolved enantiomers of ten DNP-AA racemates available for this study. However, a complete resolution of these enantiomers in one CZE run required that the effect of the chiral selector be complemented by complexing effects of polyvinyl pyrrolidone (PVP) or gamma-CD. Complexing and chiral recognition capabilities of MA-beta-CD combined with complexing effects of gamma-CD and PVP provided separating conditions suitable for the CZE separations of multicomponent mixtures of DNP-AAs with preserved resolutions of the enantiomers. For example, a mixture consisting of 43 DNP-AA constituents was resolved using an MA-beta-CD/gamma-CD combination with three peak overlaps.

Topics: alpha-Cyclodextrins; Amino Acids; beta-Cyclodextrins; Cyclodextrins; Dinitrobenzenes; Electrophoresis, Capillary; gamma-Cyclodextrins

Different authors have demonstrated the inclusion of miconazole in cyclodextrins (CD). Miconazole can be included in the CD cavity both in the neutral and in the ionized form. The present study tries to understand which fragment of the miconazole molecule is involved in the inclusion. Austin Model 1 approximate molecular orbital calculations have been performed on several complexes between beta-cyclodextrin (betaCD) or gamma-cyclodextrin (gammaCD) and miconazole in the ionized and the non-ionized forms of the two R and S enantiomers in three different orientations. We observed that betaCD is a good vehicle to transport miconazole which can be very easily released. The complexation energy between miconazole and betaCD is not very high but the entropic factor has a great incidence on the stability of the formed complex. The inclusion of the dichlorobenzene-CH(2)-O- and of the imidazole part of the S isomer gives rise to the most probable complex in acidic conditions (ionized miconazole). Nevertheless, the inclusion should be considered as a dynamic process in which different parts of the molecule could be alternatively included in betaCD. The present work demonstrates the high capability of deformation of betaCD which could easily accommodate several types of ligand. By opposite, the cycle extension in gammaCD leads to a more rigid vehicle with regards to miconazole.

Topics: Antifungal Agents; beta-Cyclodextrins; Crystallography, X-Ray; Cyclodextrins; Excipients; gamma-Cyclodextrins; Miconazole; Models, Molecular; Molecular Conformation; Thermodynamics

Native beta- and gamma-cyclodextrin bound to silica (ChiraDex-beta and ChiraDex-gamma) were packed into capillaries and used for enantiomer separation by capillary electrochromatography (CEC) under aqueous and nonaqueous conditions. Negatively charged analytes (dansyl-amino acids) were resolved into their enantiomers by nonaqueous CEC (NA-CEC). The addition of a small amount of water to the nonaqueous mobile phase enhanced the enantioselectivity but increased the elution time. The choice of the background electrolyte (BGE) determined the direction of the electroosmotic flow (EOF). With 2-(N-morpholino) ethanesulfonic acid (MES) or triethylammonium acetate (TEAA) as BGE an inverse EOF (anodic EOF) was observed while with phosphate a cathodic EOF was found. The apparent pH (pH*), the concentration of the BGE, and the nature of the mobile phase strongly influenced the elution time, the theoretical plate number and the chiral separation factor of racemic analytes.

Topics: Acetonitriles; Amino Acids; beta-Cyclodextrins; Buffers; Cyclodextrins; Dansyl Compounds; Electrolytes; Electrophoresis, Capillary; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Methanol; Osmolar Concentration; Solvents; Stereoisomerism; Water

The racemates of several chiral thiobarbiturates were separated by using different cyclodextrins in capillary electrophoresis (CE). Six neutral and negatively charged cyclodextrins 1 (CDs) were employed as chiral separators whereof five led to successful separation of enantiomeric thiobarbiturate pairs. The CDs used were the native alpha-CD, beta-CD, gamma-CD, and heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (HDM) as well as heptakis-(2,3-di-O-methyl-6-sulfato)-beta-cyclodextrin (HDMS) and heptakis-(2,3-di-O-acetyl-6-sulfato)-beta-CD (HDAS). Five of the six chiral thiobarbiturates studied could be resolved at a basic pH value of 9.4 and a phosphate buffer concentration of 100 mM in a fused-silica capillary. Structurally related substances showed a similar behavior in separation: 1 and 2 bearing the center of chirality in the side chain at C5 can be best separated using gamma-CD, the N-alkyl-substituted compounds 3 and 4 as well as the N/S-dialkyl-substituted compound 5 could be resolved with HDM. Using the neutral CDs, the migration times were relatively small (< 11 min). 3 and 4 could be also resolved by means of the negatively charged HDMS. In the latter case, the migration time is twice as long as with HDM.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; gamma-Cyclodextrins; Stereoisomerism; Thiobarbiturates

Micellar electrokinetic chromatography (MEKC) was used for the chiral separation of uncharged analytes (C- and N-protected amino acids). Sodium dodecyl sulfate (SDS) was the micelle forming agent, and different cyclodextrin (CD) derivatives were added as chiral selectors. Suitable conditions for the enantioseparation were found by variation of the separation conditions. The influence of addition of organic solvents like acetonitrile or methanol, and other chiral additives (camphor-10-sulfonic acid, malic acid) was examined. The addition of an organic modifier resulted in different effects on micelle formation, and thereby on the separation. The used chiral additives did not improve the selectivity. Furthermore, dependence of the electroosmotic flow (EOF), and the capacity factors on the concentration of CDs was investigated. Increasing the CD concentration, both the EOF to a smaller extent as well as the capacity factors decrease. Nevertheless, the enantioseparation is improved with a CD-concentration up to 30 mM. Higher CD-concentrations reduce the separation of the analytes.

Topics: Acetonitriles; Amino Acids; beta-Cyclodextrins; Chromatography, Micellar Electrokinetic Capillary; Cyclodextrins; Esters; gamma-Cyclodextrins; Indicators and Reagents; Sensitivity and Specificity; Sodium Dodecyl Sulfate; Solvents; Stereoisomerism

Native beta- and gamma-cyclodextrin (CD), neutral beta-CD derivatives and ethylcarbonate derivatives of beta- and gamma-CD were used as stereoselective additives for CD-capillary zone electrophoresis (CZE) resolution of atropisomers of 1,1'-bi-(2-naphthol) (BN). CZE experiments at variable CD concentration allowed calculating binding constants from electrophoretic mobility data, corrected for electroosmotic flow (EOF) and running buffer viscosity variations. The CDs were chosen on the basis of geometric examination of molecular models of BN and CDs that suggested the possibility of inclusion complexes formation. Optimum concentrations, with aqueous 25 mM phosphate running buffer at pH 10.5, 36 cm x 50 microm capillary and 10 kV applied potential, were 3.6, 3.9, 2.1, 2.2, 1.9 mM for beta-CD, gamma-CD, ethylcarbonate-beta-CD, methyl-beta-CD and hydroxypropyl-beta-CD, respectively.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; gamma-Cyclodextrins; Molecular Conformation; Naphthols; Stereoisomerism

Some biological properties of new bifunctional conjugates designed for drug targeting were evaluated through in vitro experiments. Eight peptidylcyclodextrin compounds were used, which correspond to modified beta- or gamma-cyclodextrin (CD) grafted on neuropeptide substance P (SP) or a shorter derivative (SP(4-11)). Using anti-SP and anti-CD antibodies as molecular probes, we showed that the main structural features of the two moieties of these adducts were preserved. Binding experiments, using CHO cells expressing the human SP-specific NK1 receptor, demonstrated the functionality of all peptidylcyclodextrin derivatives, which exhibited IC50 values in a 10(-9)-10(-7) M range. All compounds were able to induce a pharmacological response, triggering phosphatidylinositol turnover with EC50 values in the same range as the natural ligand. Moreover, autoradiography analysis of rat spinal corn sections proved that [125I]SP binding was dose-dependently displaced by one selected compound (a gamma-CD-SP), showing a similar affinity of this adduct for the rat neurokinin 1 receptor. Our observations demonstrate that these peptidylcyclodextrins efficiently target NK1 receptor-expressing cells.

Topics: Animals; Antibodies; Autoradiography; beta-Cyclodextrins; Binding, Competitive; CHO Cells; Cricetinae; Cyclodextrins; Drug Delivery Systems; Drug Design; gamma-Cyclodextrins; Molecular Structure; Receptors, Neurokinin-1; Recombinant Proteins; Substance P

The effect of dietary cyclodextrins on liver and serum lipids and cecal organic acid production was investigated. Male Wistar rats were fed a basal diet and a diet containing 5% of alpha-, beta-, or gamma-cyclodextrin. The body weight gain in rats fed the alpha-cyclodextrin diet was not significantly different from rats fed the other three kinds of diets. The feeding of dietary alpha-cyclodextrin increased total lipid and phospholipids in the liver. Beta-cyclodextrin significantly lowered serum total cholesterol and phospholipid levels compared with the basal diet et al. A decrease in serum triacylglycerol levels was also observed in beta-cyclodextrin-fed rats. Dietary alpha-cyclodextrin significantly increased the weight of cecal tissues and contents, and an approximate fourfold increase in acetate, propionate, and total organic acids was noted, indicating the fermentibility of beta-cyclodextrin compared with the basal diet. It seems likely that the suppression of serum cholesterol levels by alpha- and beta-cyclodextrins might be due to the increasing acetate and propionate productions in the cecum. cecal organic acid, cyclodextrin, serum cholesterol, rats

Topics: Acetates; alpha-Cyclodextrins; Animals; beta-Cyclodextrins; Blood Glucose; Butyrates; Cecum; Cholesterol; Cyclodextrins; Fermentation; gamma-Cyclodextrins; Lipid Metabolism; Lipids; Liver; Male; Propionates; Rats; Rats, Wistar; Succinic Acid; Triglycerides; Weight Gain

The simultaneous interaction of 15 steroidal drugs with tau-cyclodextrin (tauCD) and hydroxypropyl-beta-CD (HPbetaCD) was determined by charge transfer chromatography and the relative strength of interaction was calculated for each drug-tauCD-HPbetaCD ternary complex. The mixture of CDs interacted with each steroidal drugs decreasing the lipophilicity of the guest molecules. The chemical structure of steroidal drugs markedly influenced their capacity to interact with the mixture of CDs, the more lipophilic compounds formed stronger complexes with CDs. In the overwhelming majority of cases the stability of drug-tauCD-HPbetaCD system was higher than those of binary (drug-tauCD and drug-HPbetaCD) system indicating the probability of ternary complex formation. The data indicated that the ternary complex formation has to be taken into consideration in pharmaceutical formulations containing more than one type of CD or CD derivatives.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Chromatography, Thin Layer; Cyclodextrins; gamma-Cyclodextrins; Methanol; Regression Analysis; Solvents; Spectrophotometry, Ultraviolet; Steroids

Cyclodextrins (CDs) can be synthesized from starch by cyclodextrin glycosyltransferase (CGTase). This enzyme produces alpha-, beta- and gamma-CDs in varying proportions. In the production of cyclodextrins, purity as well as yield are important factors. A precise and reproducible method was developed and validated for the simultaneous determination of alpha-, beta-, and gamma-CDs. Optimum separation between the three CDs was achieved using a Finepak amino column with a mobile phase consisting of acetonitrile-water (70:30, v/v) at a flow rate of 1 ml/min. Detection was carried out using a differential refractive index detector. The developed method gave good chromatographic resolution of the three components with retention times of 13.16, 16.83 and 21.74 min for alpha-, beta- and gamma-CDs, respectively. The polynomial regression data for the calibration plots exhibited good linear relationship (coefficient of correlation r = 0.9987 for alpha, r = 0.9986 for beta and r = 0.9998 for gamma-CDs) over a concentration range of 2-10 mg/ml. Statistical analysis proves that the proposed LC method is precise, reproducible and accurate for the estimation of alpha-, beta- and gamma-cyclodextrins. The method can be employed for determination of percent purity as well as estimation of process yields of the cyclodextrins during the enzymatic production.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chromatography, Liquid; Cyclodextrins; gamma-Cyclodextrins; Quality Control; Reproducibility of Results; Solvents

In the present paper, linear and nonlinear models for complexation of alpha- beta- and gamma-cyclodextrin with guest molecules are developed, with the aim of free energy prediction and interpretation of the association process.. Linear and nonlinear regression is used to correlate experimental free energies of complexation with calculated molecular descriptors. Molecular modeling supports the interpretation of the results.. Highly predictive models are obtained, although the structural variability of the compounds used for their deduction is large, reaching from synthetic heterocycles to steroids and prostaglandins.. The scaled regression coefficients give insight to the complexation mechanisms, which appear to be different for the three types of cyclodextrins.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Energy Transfer; gamma-Cyclodextrins; Linear Models; Models, Molecular; Nonlinear Dynamics; Pharmaceutical Preparations; Protein Structure, Tertiary; Structure-Activity Relationship

In this study both native and chemically modified cyclodextrins (CDs) were investigated as buffer additives to improve the micellar electrokinetic capillary chromatography (MEKC) separation of endogenous bioanalytes in human urine. The following CDs were investigated: alpha, beta, gamma-CDs; hydroxypropyl-alpha-CD, hydroxypropyl-beta-CD, methylated beta-CD, sulphated beta-CD, sulphobutyl ether-beta-CD and hydroxypropyl-gamma-CD. The separations were compared to MEKC without additives. The best improvement in peak resolution and separation of urine components was observed with the sulphated beta-CD. A four-factor three-level full factorial design study was conducted on voltage, temperature, pH and sulphated beta-CD molarity. The optimum conditions were 25 mM sodium tetraborate, pH 9.5, 75 mM sodium dodecyl sulphate (SDS) and 6.25 mM sulphated beta-CD and were able to resolve 70 peaks from a urine pool in 12 min. These optimum conditions have been successfully applied to a number of clinical samples.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chromatography, Micellar Electrokinetic Capillary; Cyclodextrins; gamma-Cyclodextrins; Humans; Urine

Complex permittivities (epsilon*) for microwave radiation between 0.5 and 26 GHz have been determined for alpha-, beta-, and gamma-cyclodextrins in the solid state at room temperature. For the real component of epsilon*, maxima occur near 0.6 GHz, and the relation beta > alpha > gamma is evident across the full-frequency spectrum. Dielectric loss is significant only between 5 and 12 GHz for beta- and gamma-cyclodextrins with maxima near 7.5 GHz.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; gamma-Cyclodextrins; Microwaves; Structure-Activity Relationship

The taste and flavor of spray-dried powdered products are the most important quality factors. In the present study, molecular encapsulation in cyclodextrin was applied to prevent the loss of a hydrophobic flavor compound (l-menthol) during the drying of a droplet. beta-Cyclodextrin appeared to be a better encapsulant for menthol than alpha- and gamma-cyclodextrin. The retention of menthol increased with increasing concentration of both cyclodextrin and maltodextrin. A simple mathematical model is proposed for estimating the flavor retention. The theoretical results by this model estimated well the final retention of menthol encapsulated in a blend of beta-cyclodextrin and maltodextrin.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Drug Compounding; Freeze Drying; gamma-Cyclodextrins; Menthol; Models, Chemical; Polysaccharides; Taste

Literature values of DeltaG degrees (change in Gibbs free energy), DeltaH degrees (change in enthalpy), and TDeltaS degrees (temperature times change in entropy) for 1:1 complex formation by alpha-, beta-, and gamma-cyclodextrins constitute normally distributed populations with the following statistical parameters (all energy quantities in kcal mol(-1); n is the number of data points; mu is the population mean; sigma is the standard deviation): for alpha-cyclodextrin, n = 512, micro(DeltaG) = -2.85, sigma(DeltaG) = 1.23, micro(DeltaH) = -4.77, sigma(DeltaH) = 2.98, micro(TDeltaS) = -1.96, and sigma(TDeltaS) = 2.72; for beta-cyclodextrin, n = 415, micro(DeltaG) = -3.67, sigma(DeltaG) = 1. 37, micro(DeltaH) = -4.24, sigma(DeltaH) = 2.89, micro(DeltaS) = -0. 56, and sigma(TDeltaS) = 2.63; for gamma-cyclodextrin, n = 42, micro(DeltaG) = -3.71, sigma(DeltaG) = 1.19, micro(DeltaH) = -3.10, sigma(DeltaH) = 3.39, micro(TDeltaS) = +0.69, and sigma(TDeltaS) = 3. 29. The temperature is 298.15 K. The mean DeltaG degrees values correspond to binding constants of 123, 490, and 525 M(-1) for alpha-, beta-, and gamma-cyclodextrins, respectively.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Entropy; gamma-Cyclodextrins; Thermodynamics

The effect of some chemically modified cyclodextrins [namely, 2-hydroxypropyl-beta-, methyl-beta-, and 2-hydroxypropyl-gamma-cyclodextrin (HP-beta-CD, Me-beta-CD, and HP-gamma-CD, respectively)] on the aqueous solubility and dissolution rate of the hypnotic agent Zolpidem (ZP) was investigated. Solid complexes were prepared by freeze drying and characterized by infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. The solubility and dissolution rate of the drug were significantly improved by complexation with HP-beta-CD or Me-beta-CD. The structure of the inclusion complex ZP-HP-beta-CD in CH(3)COOD/D(2)O was investigated by (1)H and (13)C NMR spectroscopy, including NOE measurements. These measurements revealing a weak interaction between the tolyl moiety of the guest molecule and the HP-beta-CD cavity. The ataxic activity in rat was also investigated and it was found that ZP-HP-beta-CD and ZP-Me-beta-CD complexes showed almost 2-fold longer ataxic induction times than controls.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Ataxia; beta-Cyclodextrins; Cyclodextrins; gamma-Cyclodextrins; Hypnotics and Sedatives; Male; Pyridines; Rats; Rats, Sprague-Dawley; Solubility; Zolpidem

This study investigated whether hepatic metallothionein gene expression is affected by dietary cyclodextrins. Young male Wistar rats were fed a basal diet or cyclodextrin-supplemented (50 g of cyclodextrin per kg diet) diets for 7 d. Copper content in the liver did not show any significant changes among rats fed the basal, beta- and gamma-cyclodextrin diets. There were no differences in liver or serum zinc among groups. Copper content in serum was markedly decreased in rats fed the gamma-cyclodextrin-supplemented diet. Liver metallothionein mRNA levels were significantly elevated in both beta- and gamma-cyclodextrins-fed rats, but not in alpha-cyclodextrin-fed rats. Thus, the increase in hepatic metallothionein mRNA levels might be due to this mechanism except for the contents of copper and zinc in the liver.

Topics: Animals; beta-Cyclodextrins; Blotting, Northern; Copper; Cyclodextrins; gamma-Cyclodextrins; Gene Expression; Liver; Male; Metallothionein; Rats; Rats, Wistar; RNA, Messenger; Zinc

Employing capillary electrophoresis, the racemates of 29 acidic, neutral and basic dihydropyridines (DHPs) were separated by means of neutral and negatively charged cyclodextrins (CDs). Whereas the enantiomers of the acidic DHPs could be resolved with neutral CDs, mostly alpha- and beta-CD, the enantiomers of the neutral DHPs were only baseline-separated using the sulfobutyl ether-substituted beta-CD. Working in reversed polarity mode (detector at the anode) improved the peak shape and the resolution of the enantiomers. The racemates of the DHP bearing a secondary or tertiary amine function in the side chain at position 3 could be separated by using either the neutral gamma-CD or negatively charged CDs. The poor peak shape found with anionic CDs could be improved by the addition of methanol. The combination of gamma-CD and sulfated beta-CD allowed the detection of the minor enantiomer of lercanidipine (24) at less than 1% w/w.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Dihydropyridines; Electrophoresis, Capillary; gamma-Cyclodextrins; Molecular Structure

Separation of levonorgestrel, progesterone and testosterone was achieved by using micellar electrokinetic capillary chromatography (MECC). A column of 53 cm (to the detector) x 50 microns i.d. uncoated fused-silica capillary (totally 68 cm in length) and an ultra-violet detector with fixed wavelength at 254 nm were used throughout all the experiments. MECC analysis was optimized by evaluating three different micelle-forming agents, the concentration of SDS and several of organic additives in a 10 mmol/L borate running buffer (pH 9.2). Complete separations were obtained with either 10%-20% acetonitrile or 20 mmol/L 2,6-dimethyl-beta-cyclodextrin (DM-beta-CD) as the modifier in buffer. When the acetonitrile volume fraction was in the range of 0-15%, the migration times of the three steroids increased with the acetonitrile volume fraction, but in the range of 15%-20% acetonitrile concentrations, the situation was opposite. This behavior of the steroids was attributed to the interaction of two opposite effects, an increased mobility due to decreased partition coefficient and a decreased electroosmotic flow (EOF). Both beta-cyclodextrin (beta-CD) and gamma-cyclodextrin (gamma-CD) were found to be inadequate for a satisfactory separation.

Topics: beta-Cyclodextrins; Chromatography, Micellar Electrokinetic Capillary; Cyclodextrins; gamma-Cyclodextrins; Levonorgestrel; Progesterone; Testosterone

Although praziquantel (PZQ) is the primary drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery via the oral route. In spite of its poor solubility, PZQ is well absorbed across the gastrointestinal tract, but large doses are required to achieve adequate concentrations at the target sites. Improving the solubility would enable the parenteral route to be used, thereby avoiding significant first pass metabolism. The aqueous solubility of PZQ was improved by forming inclusion complexes with alpha-, beta- and gamma-cyclodextrins (CDs). These complexes were assessed and confirmed by solubility analysis, Fourier transform infrared analysis, elemental analysis, differential scanning calorimetry and mass spectrometry. Dissolution of PZQ from the alpha-, beta- and gamma-CD complexes was 2.6-, 5- and 8-fold greater, respectively, than that of the pure drug. However, only the beta-complex had a stability constant in the optimum range for pharmaceutical use, suggesting that the preferred complex for further development would be a water-soluble beta-CD derivative.

Topics: alpha-Cyclodextrins; Antiplatyhelmintic Agents; beta-Cyclodextrins; Calorimetry, Differential Scanning; Circular Dichroism; Computer Simulation; Cyclodextrins; Excipients; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Mass Spectrometry; Praziquantel; Solubility; Spectroscopy, Fourier Transform Infrared

Enantiomeric separation of 21 amino acids derivatized with fluoresceine isothiocyanate isomer I (FITC) has been studied by micellar electrokinetic chromatography using beta- and gamma-cyclodextrin (CD) as chiral selectors. Chiral resolution of 21 FITC derivatives of amino acids was achieved with both beta- and gamma-CD in 100 mM borate buffer (pH 9.5) containing 30 mM sodium dodecyl sulfate (SDS). The effects of CD concentration, SDS concentration and organic modifiers' concentration as well as capillary length were investigated. Chiral recognition capability of beta- and gamma-CD was compared. Gamma-CD was found to be a better chiral selector than beta-CD in terms of chiral resolution capability for FITC-amino acids.

Topics: 2-Propanol; Acetonitriles; Amino Acids; beta-Cyclodextrins; Chromatography; Cyclodextrins; Fluorescein-5-isothiocyanate; gamma-Cyclodextrins; Isomerism; Sodium Dodecyl Sulfate; Time Factors

Two antipsychotic drugs (clozapine and loxapine) and six metabolites, N-demethylclozapine, clozapine N-oxide, N-demethylloxapine (amoxapine), 7-hydroxyloxapine, 8-hydroxyloxapine, 8-hydroxyamoxapine, were separated by capillary zone electrophoresis. Variation of pH and ionic strength of the acidic phosphate buffer (pH below 4) did not enable the separation of loxapine and one of its metabolites. Resolution of the single parent drugs and their metabolites was possible in background electrolytes (phosphate, pH 3.5, 60 mmol/l) containing either 0.2% (w/v) polyvinylpyrrolidone as replaceable pseudo-stationary phase, or 0.75 mmol/l beta-cyclodextrin added as complex-forming agent. Full separation of the mixture with baseline resolution of all analytes was obtained with a background electrolyte with heptakis-6-sulfato-beta-cyclodextrin added as negatively charged complexation agent with improved separation selectivity.

Topics: Antipsychotic Agents; beta-Cyclodextrins; Clozapine; Cyclodextrins; Electrolytes; Electrophoresis, Capillary; gamma-Cyclodextrins; Hydrogen-Ion Concentration; Loxapine; Osmolar Concentration; Povidone

The interaction of cyclodextrins (CDs) with dipalmitoylphosphatidylcholine (DPPC) liposomes has been studied using differential scanning calorimetry (DSC). The phase transition temperature and the enthalpy change due to the gel-to-liquid crystalline phase transition of the liposomes were measured in the presence of alpha-CD, beta-CD, gamma-CD, heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD), heptakis (2,3,6-tri-O-methyl)-beta-CD (TOM-beta-CD) and 2-hydroxylpropyl beta-CD, respectively. The effects on the change of enthalpy of the transition temperature were remarkable in the order of DOM-beta-CD > alpha-CD > TOM-beta-CD. The residual CDs caused scarcely detectable changes in the enthalpy changes and the transition temperatures. In order to clarify the DSC curves in the presence of the CDs mentioned above, the type of interactions which occurred between CDs and DPPC liposomes were studied. Consequently, it was found that DOM-beta-CD forms a soluble complex and alpha-CD forms an insoluble complex with DPPC liposomes, whereas only a slight amount of TOM-beta-CD was suggested to penetrate the matrix of the liposomes.

Topics: 1,2-Dipalmitoylphosphatidylcholine; 2-Hydroxypropyl-beta-cyclodextrin; alpha-Cyclodextrins; beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclodextrins; gamma-Cyclodextrins; Liposomes; Thermodynamics

Capillary electrophoresis has been shown to be a very useful analysis technique for secondary metabolites of plants. In the present study a method is described for the qualitative and quantitative determination of ergot alkaloids and their epimers. The extraction from the biological matrix yields recoveries of 50-97%, depending on the individual alkaloid. Using a mixture of 20 mM beta-cyclodextrin (CD), 8 mM gamma-CD, 2 M urea and 0.3% (w/w) poly(vinyl alcohol) to phosphate buffer at pH 2.5 the simultaneous separation of all analytes was achieved. A 37 cm (30 cm) fused-silica capillary, at a voltage of 25 kV and a temperature of 20 degrees C, was used for the analysis. Overall analysis time for the separation was 12 min. The limit of detection of the alkaloids using UV detection at 214 nm can be improved 30-fold to about 9.10(-8) M when laser-induced fluorescence detection is applied.

Topics: beta-Cyclodextrins; Buffers; Cyclodextrins; Electrophoresis, Capillary; Ergot Alkaloids; gamma-Cyclodextrins; Phosphates; Solubility; Urea

The initial action of cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) from an alkalophilic Bacillus sp. A2-5a on amylose was investigated. Synthetic amylose was incubated with purified CGTase then terminated in the very early stage of the enzyme reaction. When the reaction mixture was treated with glucoamylase and the resulting glucoamylase-resistant glucans were analyzed with high performance anion exchange chromatography, cyclic alpha-1,4-glucans, with degree of polymerization ranging from 9 to more than 60, in addition to well known alpha-, beta-, and gamma-cyclodextrin (CD), were detected. The time-course analysis revealed that larger cyclic alpha-1, 4-glucans were preferentially produced in the initial stage of the cyclization reaction and were subsequently converted into smaller cyclic alpha-1,4-glucans and into the final major product, beta-CD. CGTase from Bacillus macerans also produced large cyclic alpha-1, 4-glucans except that the final major product was alpha-CD. Based on these results, a new model for the action of CGTase on amylose was proposed, which may contradict the widely held view of the cyclization reaction of CGTase.

Topics: alpha-Cyclodextrins; Amylose; Bacillus; beta-Cyclodextrins; Cyclodextrins; gamma-Cyclodextrins; Glucan 1,4-alpha-Glucosidase; Glucans; Glucosyltransferases

Enantiomers of disopyramide display different biological actions, and therefore chiral selective analysis is necessary. Fifteen different cyclodextrins (CDs) and CD derivatives were tested as capillary electrophoresis (CE) additives for the chiral separation of disopyramide. Eleven types of CDs showed chiral recognition features and four types had a baseline or close to baseline separation. The best resolution (Rs = 3.0) was with 15 mM carboxymethylated beta-CD (pH 4.9). A sharp decrease in the selectivity of gamma-phosphate (gamma-PhoCD) was observed in the pH range of 2-3, indicating a structural change of gamma-PhoCD. The enantiomers of disopyramide were separated in its ionized as well as neutral forms using acidic substituted CDs. The results show that the size of the CD cavity can not be used as a guide to estimate chiral separations, suggesting a more complex separation mechanism of these CDs towards disopyramide.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Disopyramide; Electrophoresis, Capillary; gamma-Cyclodextrins; Molecular Structure

A thermodynamic investigation of the hydrolysis and cyclization reactions of cyclomaltohexa-, hepta-, and octa-ose (alpha-, beta-, and gamma-cyclodextrins) has been performed using microcalorimetry and high-performance liquid-chromatography. The calorimetric measurements lead to standard molar enthalpy changes delta rHm0 (T = 298.15 K, KH2PO4 buffer (m = 0.10 mol kg-1), pH = 4.58 to 5.15) for the following reactions: alpha-cyclodextrin(aq) + 6H2O(l) = 6 D-glucose(aq), beta-cyclodextrin(aq) + 7H2O(l) = 7 D-glucose(aq), gamma-cyclodextrin(aq) + 8H2O(l) = 8 D-glucose(aq). Equilibrium constants were determined for the following generalized cyclization reactions (T = 329.6 K, 0.005 mol kg-1 K2HPO4 buffer adjusted to pH = 5.55 with H3PO4) catalyzed by cyclomaltodextrin glucanotransferase: Gu(aq) = alpha-cyclodextrin(aq) + G(u-6)(aq), Gv(aq) = beta-cyclodextrin(aq) + G(v-7)(aq), Gw(aq) = gamma-cyclodextrin(aq) + G(w-8)(aq). Here, G1 is D-glucose and the Gn's (n is a positive integer) are linear maltodextrins; u, v, and w are, respectively, integers > or = 7, > or = 8, and > or = 9. Values of the equilibrium constants, standard molar Gibbs energy change delta rGm0, standard molar enthalpy change delta rHm0, standard molar entropy change delta rSm0, and standard molar heat-capacity change delta rCp,m0 are tabulated for the above reactions at T = 298.15 K. The values of delta rGm0 and delta rSm0 for the first three above-mentioned reactions rely upon an estimated value of delta rSm0 for the hydrolysis reaction of maltose to D-glucose. The thermodynamics of the disproportionation reaction Gm(aq) + Gn(aq) = Gm-1(aq) + Gn+1(aq) is also discussed. Values of the quantities delta rHm0/N, delta rGm0/N, delta rSm0/N, and delta rCp,m0/N for the three above-mentioned hydrolysis reactions where N is the number of (1-->4)-alpha-D-glucosidic bonds broken in each of these reactions, have been calculated and compared with thermodynamic quantities for the similar hydrolysis reaction of a linear oligosaccharide.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Calorimetry; Chromatography, High Pressure Liquid; Cyclization; Cyclodextrins; gamma-Cyclodextrins; Hydrolysis; Polysaccharides, Bacterial; Thermodynamics

Differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) have been used to determine the influence of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-CyD (HP-beta-CyD) and gamma-CyD on the structural properties of the stratum corneum from the hairless mouse. Some modest changes in the stratum corneum lipid transition temperature were induced by HP-beta-CyD and blue shifts were observed in the FTIR spectra of the C-H asymmetric and symmetric stretching of the lipids from the stratum corneum. Results from TEM studies indicated that HP-beta-CyD caused removal and possible disorganization of the lipid matrix that envelopes the corneocytes of the stratum corneum, whereas no effect was seen after treatment of the samples with beta-CyD and gamma-CyD. These results suggest that HP-beta-CyD can increase the permeability of the stratum corneum possibly as a result of extraction of lipids, and might thus enhance drug permeation through the skin.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclodextrins; Epidermis; gamma-Cyclodextrins; Lipid Metabolism; Male; Mice; Mice, Hairless; Microscopy, Electron; Permeability; Skin; Spectroscopy, Fourier Transform Infrared

When 2,6-di-O-tert-butyldimethylsilylated cyclomalto-oligosaccharides (cyclodextrins) are treated with allyl or methyl iodide and NaH in dry tetrahydrofuran, O-2-->O-3 migration of the secondary 2-O-tert-butyldimethylsilyl groups occurs, leading to 2-O-alk(en)yl-3,6-di-O-tert-butyldimethylsilyl-cyclodextrin derivatives. The detection and identification of the reaction step during which migration occurred is described and possible mechanisms of migration are discussed.

Topics: Acetylation; beta-Cyclodextrins; Carbohydrate Sequence; Cyclodextrins; gamma-Cyclodextrins; Magnetic Resonance Spectroscopy; Methylglucosides; Molecular Sequence Data; Molecular Structure; Organosilicon Compounds

Two inclusion compounds, progesterone with beta- and gamma-cyclodextrin, were studied with X-ray powder diffractometry and thermal analysis. Disappearance of characteristic X-ray diffraction patterns of the two compounds as well as the appearance of a new diffraction pattern for each were found when formation of the inclusion compounds was completed. The X-ray diffraction patterns of beta-cyclodextrin measured at various temperatures showed a structural change occurring between 60 degrees C to 80 degrees C, which coincided well with the DSC endothermic peak around 75 degrees C. Results suggest that changes in the X-ray diffraction patterns of cyclodextrin during inclusion formation and during heating is due to the displacement of adsorbed water by progesterone in the cavity of cyclodextrin.

Topics: beta-Cyclodextrins; Crystallography, X-Ray; Cyclodextrins; Differential Thermal Analysis; gamma-Cyclodextrins; Progesterone

Conformations of manually built native and permethylated alpha-, beta-, and gamma-cyclodextrins (CD) were investigated using various computer assisted molecular modelling methods. Calculations were carried by applying the MM+ and the Tripos force field. The influences of atomic charges on the macrocyclic conformations during the optimization procedure were analyzed. The permethylation of hydroxyl groups of cyclodextrins changes bond and torsion angles between the glucose monomers and of the primary substituents. A method to determine the diameters of the cyclodextrin cavity by a modelling approach is described. It is shown that due to permethylation the larger cavity opening is increased and the primary substituents are canted outwards. As a consequence, the torus shape of the molecule changes, which is an important feature for docking and fitting studies.

Topics: Algorithms; alpha-Cyclodextrins; beta-Cyclodextrins; Carbohydrate Conformation; Carbohydrate Sequence; Computer Simulation; Cyclodextrins; gamma-Cyclodextrins; Glycosides; Methylation; Models, Molecular; Molecular Sequence Data

Capillary zone electrophoresis (CZE) methods with indirect absorbance detection for analyzing mixtures of alpha-, beta-, and gamma-cyclodextrins (CDs) and their derivatives have been developed. Benzylamine, salicylic, sorbic, or 1-naphthylacetic acid (NAA) was utilized as background electrolyte (BGE) and absorbance provider. Separation of alpha-, beta-, and gamma-CD could be achieved in less than 18 min when the CZE was run in 2 mM NAA or 5 mM sorbate solution (pH 12.2) and detected by indirect absorbance at 222 or 254 nm, respectively. Mixtures of alpha- and beta-CDs, and dimethyl- and trimethyl-derivatives of beta-CD could also be analyzed by CZE, using 50 mM salicylic acid or benzylamine solution (pH 6.0) as BGE with indirect absorbance detection at 230 and 210 nm, respectively. CZE methods for determining the inclusion complex formation constants of various CDs for salicylic acid or benzylamine with either direct or indirect absorbance detection have also been developed. The formation constants of salicylate are in the range from ca. 8 +/- 0.3 mole-1 for the complex with alpha-CD to ca. 99 +/- 2 molarity-1 for the complex with methyl-beta-CD. The detection limits (determined at a signal-to-noise ratio of 3) for the NAA and the salicylate system are ca. 0.1 mM and 1 mM, respectively.

Topics: alpha-Cyclodextrins; Benzylamines; beta-Cyclodextrins; Cyclodextrins; Electrolytes; Electrophoresis, Capillary; gamma-Cyclodextrins; Naphthaleneacetic Acids; Salicylates; Salicylic Acid; Sorbic Acid

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Carbohydrate Sequence; Cyclodextrins; gamma-Cyclodextrins; Glycosides; Molecular Sequence Data; Oligosaccharides

Molecular modeling has been used to study the complexation between alpha, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. The computer program SYBYL 5.3 and the Tripos force field (version 5.2) were used for all the calculations. Three-dimensional structures of 13 amine compounds were built individually from their atoms, and CDs were built based on the X-ray crystallographic coordinates. The diphenylmethyl derivative-CD complexes were constructed and optimized. Based on the calculated binding energies accompanying the inclusion process, the preferred method of approach of the compounds to the cavities of the CD molecules, and the structural effects on the binding between amine compounds and three CDs were explored. The calculated binding energies exhibited a good correlation with the stability constants obtained from solution calorimetric titrations. The present study shows that for similar ligand molecules, the molecular modeling technique should enable us to visualize the structure of the inclusion complexes and will also assist us in determining the ability of a potential drug molecule to form a stable complex with CDs.

Topics: alpha-Cyclodextrins; Amines; beta-Cyclodextrins; Biphenyl Compounds; Calorimetry; Chemical Phenomena; Chemistry, Physical; Cyclodextrins; gamma-Cyclodextrins; Models, Molecular; Software; X-Ray Diffraction

Interaction of cyclodextrins with native and isolated lipoproteins was studied by electrophoretic and spectroscopic means. Reaction between these two biomolecules resulted in the formation of soluble and insoluble complexes. Cyclodextrin-mediated precipitation of lipoproteins was strongly affected by the concentration of the oligosaccharide and the presence of guest molecules capable of being entrapped within the cyclodextrin cavity. Lipoprotein precipitation by cyclodextrins was observed under acidic, neutral as well as alkaline conditions. The ionic strength of the medium did not significantly affect this interaction. Under appropriate experimental conditions, most types of cyclodextrins were able to form complexes with the various lipoprotein classes. The ability of cyclodextrins to precipitate lipoproteins was in the order of beta-cyclodextrin greater than alpha-cyclodextrin greater than gamma-cyclodextrin and hydroxyalkylated beta-cyclodextrin. Among the lipoproteins, the order of reactivity with a given cyclodextrin was: low density lipoproteins greater than high density lipoproteins greater than very low density lipoproteins. Competitive studies using L-phenylalanine and methanol, both of which form inclusion complexes with cyclodextrins, reveal that molecular encapsulation plays an important role in the stabilization of beta-cyclodextrin-lipoprotein complexes. The present data also suggests that the binding of cyclodextrins to lipoproteins may involve the formation of exclusion complexes.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Binding, Competitive; Chemical Precipitation; Cyclodextrins; Electrophoresis, Agar Gel; gamma-Cyclodextrins; Humans; Hydrogen-Ion Concentration; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Methanol; Osmolar Concentration; Phenylalanine

Alpha-, beta- and gamma-cyclodextrins are cyclic hexamers, heptamers, and octamers of glucose, respectively, and thus are hydrophilic; nevertheless, they have the ability to solubilize lipids through the formation of molecular inclusion complexes. The volume of lipophilic space involved in the solubilization process increases with the number of glucose units in the cyclodextrin molecule and, consequently, cyclodextrins were found to have different effects on human erythrocytes: (a) in the induction of shape change from discocyte to spherocyte the potency was observed to be alpha greater than gamma, but with beta-cyclodextrin hemolysis occurred before the change was complete; (b) in the increase of fluorescence intensity of 1-anilinonaphthalene-8-sulfonate in cyclodextrin-pretreated membranes, the observed potency was beta much greater than gamma greater than alpha; (c) in the release of potassium and hemoglobin, the potency was beta greater than alpha greater than gamma. The potencies of cyclodextrin for solubilizing various components of erythrocytes were alpha greater than beta much greater than gamma for phospholipids, beta much greater than gamma greater than alpha for cholesterol and beta much greater than gamma greater than alpha for proteins. The solubilization potencies were derived from concentration/final-effect curves. The above processes occurred without entry of solubilizer into the membrane, since (a) beta-[14C]cyclodextrin did not bind to erythrocytes and (b) cyclodextrins did not enter the cholesterol monolayer. A study of the [3H]cholesterol in erythrocytes indicated that beta-cyclodextrin extracted this lipid from membrane into a new compartment located in the aqueous phase which could equilibrate rapidly with additional erythrocytes. Therefore, the effects of cyclodextrins differ from those of detergents which first incorporate themselves into membranes then extract membrane components into supramolecular micelles.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Dextrins; Erythrocyte Membrane; Erythrocytes; gamma-Cyclodextrins; Humans; Membrane Lipids; Membrane Proteins; Starch; Structure-Activity Relationship

The alkylation of cyclomalto-oligosaccharides (cyclodextrins, CDs) with dialkyl sulfate-barium hydroxide has been claimed to yield 2,6-di-O-alkyl derivatives. Re-investigation by plasma desorption-m.s. of the products of laboratory methylation of alpha CD, beta CD, or gamma CD and ethylation of beta CD and several commercial preparations revealed them to be mixtures with broad and roughly symmetrical distributions of the degree of substitution. Recrystallization separated the components only partially. Analysis of the product of methylation of a mixture of CDs established the order of reactivity gamma much greater than alpha greater than or equal to beta. The reactivity of gamma CD thus resembles that of amylose.

Topics: Alkylation; alpha-Cyclodextrins; Barium; Barium Compounds; beta-Cyclodextrins; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Mass Spectrometry; Methylation; Starch; Sulfuric Acid Esters; Sulfuric Acids

Forskolin, a diterpene which displays a potent IOP-lowering activity in several animal species, is very poorly water soluble. This characteristic imposes the ocular administration of the drug as a suspension, a type of formulation which may present several preparative and biological disadvantages, such as e.g. difficulty of sterilization and poor bioavailability. The present report is concerned with an investigation on the solubilization of forskolin by some eye-compatible polymeric agents. While beta- and gamma-cyclodextrin were not particularly effective solubilizers, one polyoxyethylene-polyoxypropylene block copolymer (PluronicR F-127) increased 40 times the drug solubility in water (c. 120 mg/100 ml vs. c. 3 mg/100 ml). When tested on rabbits with artificially increased IOP, the Pluronic vehicle prolonged significantly the duration of the hypotensive activity of forskolin with respect to a standard 1.0% suspension of the drug. The potential of these alternative formulations for increasing the ocular bioavailability of forskolin is discussed.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Colforsin; Cyclodextrins; gamma-Cyclodextrins; Intraocular Pressure; Male; Ocular Hypertension; Poloxalene; Rabbits; Solubility; Solutions

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; gamma-Cyclodextrins; Vinca Alkaloids

Cyclodextrins catalyzed the inactivation of sarin and soman but did not inactivate tabun and VX. Furthermore, sarin and soman showed greater affinity for beta-cyclodextrin than for alpha- or gamma-cyclodextrins. Thus beta-cyclodextrin appears to be an attractive starting material for the preparation of a catalyst able to inactivate sarin and soman more effectively. Such a catalyst might contribute to improving the therapy of poisoning caused by these two nerve agents.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Kinetics; Organophosphates; Organophosphorus Compounds; Organothiophosphorus Compounds; Sarin; Soman; Starch

Topics: Animals; beta-Cyclodextrins; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Ointments; Permeability; Prednisolone; Rats; Skin Absorption; Starch

The effects of beta- and gamma-cyclodextrins (CyDs) on the pharmacokinetic behavior of prednisolone after intravenous or intramuscular administration in rabbits were investigated. The serum levels of prednisolone after intravenous administration were little affected by the two CyD complexes. This might have been due to the rapid dissociation of the complexes in the large volume of body fluid. On the other hand, the serum levels of prednisolone after intramuscular administration of the CyD complexes in the form of a suspension to rabbits were significantly higher than those of the drug alone. In addition, the mean residence times of both CyD complexes were shorter than that of prednisolone alone. In contrast, there was little or no difference in pharmacokinetic parameters after intramuscular administration of the drug in the form of a solution except for Tmax between prednisolone and its CyD complexes. The enhanced rate of bioavailability of prednisolone after intramuscular administration in the form of a suspension may be due to the rapid dissolution of CyD complexes.

Topics: Animals; beta-Cyclodextrins; Biological Availability; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Injections, Intramuscular; Injections, Intravenous; Male; Prednisolone; Rabbits; Starch

The 4,6,8(14)-triene-3-one steroids, highly fluorescent in aqueous solutions, lose their fluorescence power when binding occurs to hydrophobic regions of other molecules, such as the hydrophobic cavity in the ring system of cyclodextrins. The fluorescence intensity decreases almost completely when beta- and gamma-cyclodextrins are present in the solution. Scatchard plots derived from fluorescence titrations show that one or two molecules of steroid bind to one cyclodextrin molecule with KD,F-values of about 10(-4)-10(-5) mol/liter. Temperature-jump experiments show a single relaxation process, with rate constants for the decay of the beta-cyclodextrin-steroid complexes of about 10(4)-10(5) per s. For alpha- and gamma-cyclodextrins such relaxation processes are not observed.

Topics: 17-alpha-Hydroxyprogesterone; alpha-Cyclodextrins; Androstatrienes; beta-Cyclodextrins; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Hydroxyprogesterones; Kinetics; Pregnatrienes; Protein Binding; Spectrometry, Fluorescence; Starch; Testosterone

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Prednisolone; Solutions; Starch

Topics: beta-Cyclodextrins; Betamethasone; Chemistry, Pharmaceutical; Cyclodextrins; Dextrins; gamma-Cyclodextrins; Ointment Bases; Starch

Topics: Animals; beta-Cyclodextrins; Biological Availability; Cyclodextrins; Dextrins; Dogs; gamma-Cyclodextrins; Male; Spironolactone; Starch