betadex and carboxymethyl-beta-cyclodextrin

Carboxymethyl-β-cyclodextrins (CM-β-CDs) with five kinds of degrees of substitution were synthesized and characterized. Analytical enantioseparation of six basic drugs containing N-alkyl groups, including pheniramine, chlorpheniramine, labetalol, propranolol, venlafaxine, and trans-paroxol, was achieved by reversed-phase high-performance liquid chromatography (RP-HPLC) using the synthesized CM-β-CD as chiral mobile phase additives. Key influence factors were optimized, including organic modifier, pH value, CM-β-CD with different degrees of substitution, and concentration of CM-β-CD. The mobile phase was composed of methanol and 10 mmol L

Topics: beta-Cyclodextrins; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Indicators and Reagents; Stereoisomerism

Topics: beta-Cyclodextrins; Curcumin; Humans; Hydrogels; Methacrylates; Wound Healing

A rapid and efficient method was developed for enantioseparation of basic drugs, using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral mobile phase additive, rather than involving costly chiral column in high-performance liquid chromatography (HPLC) system. Four of the six basic drug enantiomers investigated were successfully separated. The highest resolution reaches 2.15 for threo-(1S,2S)-2-amino-l-p-nitrophenyl-1,3-propanediol. The effects of the organic modifier, pH value, concentration of chiral additive, column temperature, and flow rate of mobile phase on the enantioseparation of analytes were researched. The apparent formation constants of inclusion and the thermodynamic parameters were evaluated to explain the mechanism of chiral recognition.

Topics: beta-Cyclodextrins; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Stereoisomerism

In this study, chitosan nanoparticles (HF-CD NPs) were synthesized by an ionic gelation method using negatively charged carboxymethyl-β-cyclodextrin and positively charged 2-hydroxypropyltrimethyl ammonium chloride chitosan bearing folic acid. The surface morphology of HF-CD NPs was spherical or oval, and they possessed relatively small particle size (192 ± 8 nm) and positive zeta potential (+20 ± 2 mV). Meanwhile, doxorubicin (Dox) was selected as model drug to investigate the prepared nanoparticles' potential to serve as a drug delivery carrier. The drug loading efficiency of drug-loaded nanoparticles (HF-Dox-CD NPs) was 31.25%. In vitro release profiles showed that Dox release of nanoparticles represented a pH-sensitive sustained and controlled release characteristic. At the same time, the antioxidant activity of nanoparticles was measured, and chitosan nanoparticles possessed good antioxidant activity and could inhibit the lipid peroxidation inside the cell and avoid material infection. Notably, CCK-8 assay testified that the nanoparticles were safe drug carriers and significantly enhanced the antitumor activity of Dox. The nanoparticles possessed good antioxidant activity, pH-sensitive sustained controlled release, enhanced antitumor activity, and could be expected to serve as a drug carrier in future with broad application prospects.

Topics: Antioxidants; beta-Cyclodextrins; Chitosan; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Hydrogen-Ion Concentration; Nanoparticles

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine-zeolitic imidazolate framework-8 (His-ZIF-8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral selector was chemically bonded to the His-ZIF-8@capillary column. The prepared CM-β-CD@His-ZIF-8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM-β-CD@capillary column without His-ZIF-8, the CM-β-CD@His-ZIF-8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (R

Topics: Amlodipine; Atenolol; beta-Cyclodextrins; Capillary Electrochromatography; Histidine; Propranolol; Stereoisomerism; Zeolites

Topical drug delivery system to the posterior segment of the eye is facing many challenges, such as rapid drug elimination, low permeability, and low concentration at the targeted sites. To overcome these challenges, Multifunctional nanocomposite eye drops of dexamethasone-carboxymethyl-β-cyclodextrin@layered double hydroxides-glycylsarcosine (DEX-CM-β-CD@LDH-GS) were developed for relay drug delivery. Herein, our studies demonstrated that DEX-CM-β-CD@LDH-GS could penetrate through human conjunctival epithelial cells with an intact structure and exhibited integrity in the sclera of rabbits' eyes with in vivo fluorescence resonance energy transfer imaging. Consequently, tissue distribution indicated that DEX-CM-β-CD@LDH-GS nanocomposite eye drops could maintain the effective therapeutic concentration of DEX in choroid-retina within 3 h. As a relay drug delivery system, drug-CD@LDH nanocomposites offer an efficient strategy for drug delivery from ocular surface to the posterior segment.

Topics: Animals; beta-Cyclodextrins; Cornea; Dexamethasone; Dipeptides; Drug Carriers; Drug Liberation; Hydroxides; Nanocomposites; Ophthalmic Solutions; Optical Imaging; Rabbits

Enantioselective open tubular capillary electrochromatography with carboxymethyl-β-cyclodextrin conjugated gold nanoparticles as stationary phase was developed. This novel open tubular column was fabricated through layer-by-layer self-assembly of gold nanoparticles on a 3-mercaptopropyl-trimethoxysilane-modified fused-silica capillary and subsequent surface functionalization of the gold nanoparticles through self-assembly of 6-mercapto-β-cyclodextrin. The 6-mercapto-β-cyclodextrin was firstly synthesized and determined by extensive spectroscopic data. Scanning electron microscopy, energy dispersive X-ray analysis spectroscopy, and electroosmotic flow experiments were carried out to characterize the prepared open tubular column. Then, the separation effectiveness of the open tubular column was verified by two pairs of ɑ-tetralones derivatives enantiomers and two pairs of basic drug enantiomers (tramadol hydrochloride and zopiclone) as mode analytes. Factors that influence the enantioseparation were optimized, and under the optimized conditions, satisfactory separation results were obtained for the four enantiomers: compound A, compound B, tramadol hydrochloride, and zopiclone with resolutions of 3.79, 1.56, 1.03, 1.60, respectively. For the combination of gold nanoparticles and negatively charged carboxymethyl-β-cyclodextrin, the open tubular column exhibited wider separation range for neutral and basic drugs. Moreover, the repeatability and stability of the column were studied through the run-to-run and day-to-day investigations.

Topics: Azabicyclo Compounds; beta-Cyclodextrins; Capillary Electrochromatography; Gold; Metal Nanoparticles; Molecular Structure; Particle Size; Piperazines; Stereoisomerism; Surface Properties; Tetralones; Tramadol

Lignin is the second most abundant natural biomacromolecule. A new surface-modification for nano-hydroxyapatite (n-HA) by carboxymethyl β-cyclodextrin (CM-β-CD) and lignin and its reinforce effect for poly(lactide-co-glycolide) (PLGA) were investigated by Fourier transformation infrared (FTIR), X-ray diffraction pattern (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), dispersion images, the tensile tests, scanning electron microscope (SEM), differential scanning calorimeter (DSC) and polarized optical microscopy (POM), compared to the singled-modification of CM-β-CD or lignin. The results showed that the appropriate combined-modified n-HA displayed excellent synergistic effects for increasing the dispersion, yielding good interfacial bonding between n-HA with PLGA matrix. The tensile strength of the composite was still 14.53% higher than that of PLGA, for a n-HA addition amount of 15 wt%, which was significantly better than that for the singled-modified n-HA. Additionally, in vitro degradation behavior was evaluated by soaking in simulated body fluid (SBF), and their cell response was carried out by interaction tests with bone mesenchymal stem cells. The results indicated that the combined-modification method promoted good degradation behavior and apatite deposition, as well as excellent cell biocompatibility. This study may offer an important guidance to obtain PLGA-based composites reinforced by surface-modified n-HA as bone materials.

Topics: Animals; beta-Cyclodextrins; Biocompatible Materials; Bone and Bones; Cells, Cultured; Durapatite; Lignin; Mesenchymal Stem Cells; Mice; Nanocomposites; Nanoparticles; Polyglactin 910; Tensile Strength; X-Ray Diffraction

In this study, the cyclodextrin polypeptide (R8-CMβCD) was successfully synthesized by the conjugation of a cell-penetrating peptide (R8) with carboxymethyl-β-cyclodextrin (CMβCD) via the carbon diamine reaction. Then, paclitaxel-loaded nanoparticles (PTX@R8-CMβCD NPs) was prepared. Results of transmission electron microscopy (TEM) showed that PTX@R8-CMβCD NPs were spherical with smooth surfaces and an average diameter about 144 nm. The amount of PTX released from NPs was less than 20% at pH7.4, but it increased significantly to 80% in the weakly acidic cytoplasm of tumors (pH5.0). Furthermore, PTX@R8-CMβCD NPs promoted the cellular uptake of PTX. Further studies on the mechanism showed that cellular uptake of PTX@R8-CMβCD NPs could rely on multiple pathways. In addition, the NPs had the ability to inhibit P-gp efflux pumps. Cytotoxicity tests showed that the NPs had no side effects. Taken together, PTX@R8-CMβCD NPs is an effective anticancer drug delivery system, and the material (R8-CMβCD) may be a promising anti-cancer drug carrier.

Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line; Cell Line, Tumor; Cell-Penetrating Peptides; Cyclodextrins; Drug Delivery Systems; HEK293 Cells; Humans; MCF-7 Cells; Mice; Multifunctional Nanoparticles; Neoplasms; Paclitaxel; Peptides

In the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness-changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different β-cyclodextrin derivatives. As chiral selectors, native β-cyclodextrin as well as three of its derivatives namely acetyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and carboxymethyl-β-cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of β-cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra- and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Alkaloids; beta-Cyclodextrins; Electrophoresis, Capillary; Pyrrolidines; Stereoisomerism

This work shows that the metal organic framework (MOF) HKUST-1 of type Cu

Topics: Amlodipine; beta-Cyclodextrins; Capillary Electrochromatography; Metal-Organic Frameworks; Metoprolol; Propanolamines; Propranolol; Sotalol; Stereoisomerism

In this study, magnetic nanoparticles functionalized with carboxylated β-cyclodextrin (CM-β-CD; referred to Fe

Topics: Animals; beta-Cyclodextrins; Cholesterol; Egg Yolk; Ferrous Compounds; Magnetite Nanoparticles; Microscopy, Electron, Transmission; Milk; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; X-Ray Diffraction

Gene therapy is an expanding field and it can treat genetic and acquired diseases.. It was found that formulations with DNA: CM-β-CD (Carboxymethyl-beta-cyclodextrin): Pluronic-F127 1:3:3 and 1:3 DNA: CM-β-CD are the most stable formulations indicating high incorporation of DNA within CM-β -CD.. Gel electrophoresis revealed DNA with low CM-β -CD concentration has formed a more stable complex. Samples 1:3 DNA: CM-β-CD and 1:3:3 DNA: CM-β-CD: Pluronic-127 show no DNA fragment, suggesting good condensation of DNA inside cyclodextrin cavity.. This was confirmed by fluorescence data where fluorescence intensity was reduced for samples DNA: CM-β-CD 1:3. Overall, the findings showed that Carboxymethyl-beta-cyclodextrin (as a novel non-viral gene vector) was able to provide condensation and protection to the DNA, with and without Pluronic-F127, at low concentration.. pDNA/CM-β-CD complex has not only shown to be able to transfect COS 7 and SHSY5Y cell lines, but it gives a higher transfection efficiency than that produced by the TransIT-LT1 commercial transfection reagent.

Topics: Animals; beta-Cyclodextrins; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; DNA; Electrophoresis, Agar Gel; Fluorescence; Gene Transfer Techniques; Humans; Poloxamer; Transfection

Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of β-CDs, α-CDs, and γ-CDs. Substitutions with hydroxypropyl or carboxymethyl group attenuated cytotoxicity compared with the native CDs, whereas CDs substituted with methyl groups exhibited cytotoxicity that was similar to that of the native CDs. The lipid components in blood exerted remarkable hemolysis-alleviating effects in methyl-β-CD-induced hemolysis. Occupancy of the CD cavity with cholesterol or a structurally related lipid molecule abrogated the cytotoxic capacity of the CDs. Interestingly, hydroxypropyl-γ-CD (HPγCD) was able to reduce intracellular cholesterol accumulation in Niemann⁻Pick disease type C (NPC) patient-derived fibroblasts as efficiently as HPβCD. Proteomic study indicated that HPβCD and HPγCD treatments altered the expression pattern of cellular proteins, suggesting that some of the CD-induced cellular proteins may play an important function in modulating intracellular cholesterol homeostasis.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Cell Line; Cell Survival; Cholesterol; Cyclodextrins; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Humans; Jurkat Cells; Lipid Metabolism; Membrane Lipids; Molecular Structure; Niemann-Pick Disease, Type C; Proteomics; Toxicity Tests

A new strategy is reported for the synthesis of label-free fluorescent mesoporous silica (MS) by the introduction of fluorescent carbon dots in the MSs (MSCDs) in this work. Etoposide (ETO) loaded MSCDs have been used as a drug model. Carboxymethyl β-cyclodextrin (CβCD) used as a gatekeeper agent was attached to amine-functionalized MSCDs to retain ETO molecules inside the nanocarrier. In order to target the nanocarrier to the site of action, folic acid (FA) was grafted onto the MSCDs surface (FA-CβCD-MSCDs). The in vitro release of an entrapped ETO from the formulation in phosphate buffered saline (PBS) (pH 7.4) and citrate buffer (pH 5.4) was investigated. At neutral pH in PBS, the pores are blocked by CβCD which prevent premature ETO release. However, under the weakly acidic intercellular environment of the tumor, the amide bond can be partially hydrolyzed and consequently lead to the ETO release from the nanocarrier. The targeted and ETO-loaded FA-CβCD-MSCDs showed a higher growth inhibition towards FA-positive HeLa cells compared with FA-negative HepG2 cells, as demonstrated by comparison of in vitro cytotoxicity experiments. In addition, the CDs emission was used for the fluorescent microscopic imaging. Moreover, molecular docking and molecular dynamics simulations (MDS) were applied to examine the interactions of ETO molecules with the topoisomerase II (Top II). ETO molecules bind Top II with overall binding constants of 3.08 × 10

Topics: beta-Cyclodextrins; Carbon; Drug Delivery Systems; Etoposide; Folic Acid; HeLa Cells; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Molecular Docking Simulation; Nanoparticles; Silicon Dioxide

In this paper, a new oral insulin formulation, insulin-loaded carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles (insulin/CMCD-g-CS NPs), was fabricated by ionic crosslinking technique. The therapeutic efficacy of new formulation was investigated in detail. Firstly, the CMCD-g-CS was synthesized by EDC-mediated esterification reaction. The prepared CMCD-g-CS exhibited favourable loading capacity and encapsulation efficiency of drug. The release experiment in vitro showed that the nanocarrier could efficiently protect encapsulated insulin at simulated gastric environment and release drug in the simulated colonic fluid. The insulin/CMCD-g-CS NPs effectively promoted drug internalization into Caco-2 cells and could reversibly open the tight junction between cells. The oral administration of insulin/CMCD-g-CS NPs could lastingly decrease blood sugar level in diabetic mice. The liver function study verified that the insulin/CMCD-g-CS NPs had not obvious toxicity to experimental mice. Therefore, the CMCD-g-CS could be an effective and safe oral insulin delivery carrier for future clinical application. A new biocompatible polysaccharide nanoparticle was fabricated as oral insulin delivery carrier for improving diabetic treatment.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Caco-2 Cells; Chitosan; Diabetes Mellitus, Experimental; Drug Carriers; Drug Liberation; Humans; Insulin; Male; Mice

In this work, the synthesis, characterization, and chiral capillary electrophoretic study of heptakis-(2,3-di-O-methyl-6-O-carboxymethyl)-β-CD (HDMCM), a single-isomer carboxymethylated CD, are presented. The pH-dependent and selector concentration-dependent enantiorecognition properties of HDMCM were investigated and discussed herein. The enantioseparation was assessed applying a structurally diverse set of noncharged, basic, and zwitterionic racemates. The increase in the selector concentration and gross negative charge of HDMCM improved the enantioseparation that could be observed in the majority of the cases. HDMCM was also successfully applied as BGE additive in NACE using a methanol-based system in order to prove the separation selectivity features and to highlight the broad applicability of HDMCM. Over 25 racemates showed partial or baseline separation with HDMCM under the conditions investigated, among which optimal enantiomer migration order was found for the four stereoisomers of tadalafil, tapentadol, and dapoxetine, offering the possibility of a chiral CE method development for chiral purity profiling of these drugs.

Topics: beta-Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Methanol; Pharmaceutical Preparations; Stereoisomerism

Herein we present the enantioseparation of 10 cardiovascular agents and six bronchiectasis drugs including propranolol, carteolol, metoprolol, atenolol, pindolol, esmolol, bisoprolol, bevantolol, arotinolol, sotalol, clenbuterol, procaterol, bambuterol, tranterol, salbutamol and terbutaline sulfate using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector. To our knowledge, there is no literature about using CM-β-CD for separating carteolol, esmolol, bisoprolol, bevantolol, arotinolol, procaterol, bambuterol and tranterol. During the course of work, changes in pH, CM-β-CD concentration, buffer type and concentration were studied in relation to chiral resolution. Excellent enantiomeric separations were obtained for all 16 compounds, especially for procaterol. An impressive resolution value, up to 17.10, was obtained. In particular, most of them achieved rapid separations within 20 min. Given the fact that enantioseparation results rely on analytes' structural characters, the possible separation mechanisms were discussed. In addition, in order to obtain faster separation for propranolol enantiomers in practical application, the effective length of capillary was innovatively shortened from 45 to 30 cm. After the validation, the method was successfully applied to the enantiomeric purity determination of propranolol in the formulation of drug substances.

Topics: beta-Cyclodextrins; Bronchodilator Agents; Cardiovascular Agents; Electrophoresis, Capillary; Limit of Detection; Linear Models; Propanolamines; Reproducibility of Results; Stereoisomerism

The racemic mixture of pomalidomide (POM), a second-generation immunomodulatory uncharged drug, was separated into enantiomers by capillary zone electrophoresis for the first time. Seven different chargeable cyclodextrin (CD) derivatives were screened as complexing agents and chiral selectors, investigating the stability of the POM-CD inclusion complexes and their enantiodiscriminating capacities. Based on preliminary experiments, carboxymethyl-β-CD (CM-β-CD) was found to be the most effective chiral selector. Factors influencing enantioseparation were systematically optimized, using an orthogonal experimental design. Optimal parameters (background electrolyte [BGE]: 50 mM Tris-acetate buffer, pH 6.5, containing 15 mM CM-β-CD; capillary temperature: 20°C; voltage applied +15 kV) allowed baseline separation of POM enantiomers with a resolution as high as 4.87. The developed method was validated, in terms of sensitivity (limit of detection and limit of quantification), linearity, accuracy, repeatability, and intermediate precision.

Topics: beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Stereoisomerism; Thalidomide

Near-infrared (NIR) light triggered photodynamic therapy (PDT), based on upconversion nanoparticles (UCNPs), has attracted great attention because of its high tissue penetration and low photodamage to living organisms. However, most UCNPs cannot be stably dispersed in aqueous solution and cannot carry photosensitive drugs directly. Besides, UCNP mediated PDT is a fluorescence resonance energy transfer (FRET) process from the UCNPs to the attached photosensitive drugs. So the drug and UCNPs must be stably connected and close enough. In this manuscript, carboxymethyl-β-cyclodextrin (COOH-β-CD) was used to connect UCNPs and adamantine modified phthalocyanine (Ad-ZnPc) through a self-assembly process followed by a host-guest interaction. COOH-β-CD can provide good water solubility of the system and short-distance linking between the UCNPs and Ad-ZnPc. Most importantly, the system has a strong NIR light triggered PDT activity toward cancer cells.

Topics: Adamantane; Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Drug Carriers; HeLa Cells; Humans; Indoles; Infrared Rays; Isoindoles; Models, Molecular; Molecular Conformation; Nanoparticles; Photosensitizing Agents; Solubility; Spectrometry, Fluorescence; Water

Self-assembling peptide based hydrogels have a wide range of applications in the field of tissue repair and tissue regeneration. Because of its physicochemical properties, (RADA)4 has been studied as a potential platform for 3D cell culture, drug delivery, and tissue engineering. Despite some small molecule and protein release studies with this system, there is a lack of work investigating the controlled release of hydrophobic compounds (i.e., anti-inflammatory, anticancer, antibacterial drugs, etc.) that are important for many clinical therapies. Attempts to incorporate hydrophobic compounds into self-assembling matrices usually inhibited nanofiber formation, rather resulting in a peptide-drug complex or microcrystal formation. Herein, a self-assembling chitosan/carboxymethyl-β-cyclodextrin nanoparticle system was used to load dexamethasone, which formed within a self-assembling (RADA)4 nanoscaffold matrix. Nanoparticles dispersed within the matrix were stabilized by the nanofibers within. The in vitro release of dexamethasone from the hybrid system was observed to be pH sensitive. At pH 7, release was observed for more than 8 days, with three distinct kinetic domains in the first 6 days. Data suggest that the deprotonation of chitosan at a solution pH > 6.8 leads to nanoparticle dissociation and ultimately the release of dexamethasone from the hybrid system. This system has the potential to form a multifunctional scaffold that can self-assemble with the ability to control the release of hydrophobic drugs for a wide variety of applications.

Topics: beta-Cyclodextrins; Chitosan; Delayed-Action Preparations; Dexamethasone; Drug Carriers; Hydrogels; Hydrophobic and Hydrophilic Interactions; Nanofibers; Nanoparticles; Tissue Engineering; Tissue Scaffolds

A recycling high-speed countercurrent chromatography protocol was proposed for the enantioseparation of brompheniramine by employing β-cyclodextrin derivatives as a chiral selector. The two-phase solvent system of n-hexane/isobutyl acetate/0.10 mol/L phosphate buffer solution with a volume ratio of 2:4:6 was selected by a series of extraction experiments. Factors that affected the distribution of the enantiomers over the two-phase system (e.g., the type and concentration of β-cyclodextrin derivatives = pH value of the aqueous solution, and the separation temperature) were also investigated. In addition, the theory of thermodynamics is applied to verify the feasibility of the enantioseparation process and the corresponding results demonstrate that this separation process is feasible. The optimized conditions include carboxymethyl-β-cyclodextrin concentration of 0.010 mol/L, pH of 7.5, and temperature of 5°C. Under the optimal conditions, the purities of both monomer molecules were over 99%, and the recovery yields were 88% for (+)-brompheniramine and 85% for (-)-brompheniramine, respectively.

Topics: beta-Cyclodextrins; Brompheniramine; Countercurrent Distribution; Molecular Structure; Stereoisomerism; Thermodynamics

A novel aqueous two-phase system (ATPS) composed of β-cyclodextrin (β-CD) derivative and acetone was developed for enantioselective extraction of racemic phenylsuccinic acid (PSA). Binodal curves, tie-lines, and critical points for the investigated ATPS were determined and the experimental tie-lines data were successfully correlated by Othmer-Tobias, Bancroft, and Setschenow-type equations. ATPS containing sulfobutyl ether-β-CD (SBE-β-CD) exhibited better enantioselectivity than that using carboxymethyl-β-CD (CM-β-CD). To optimize enantioselective partitioning conditions of PSA in acetone/SBE-β-CD ATPS, three factors (PSA concentration, pH, and equilibrium temperature) were analyzed by using central composite design in response surface methodology. The calculated equilibrium constants of inclusion complexation are 1638.64M

Topics: Acetone; Algorithms; beta-Cyclodextrins; Hydrogen-Ion Concentration; Models, Chemical; Stereoisomerism; Succinates

Selective enrichment of glycopeptides prior to mass spectrometry (MS) analysis is essential due to the low abundance of the modified glycopeptides in complex samples, ion suppression effects during MS ionization and detection caused by the co-presence of non-glycosylated peptides, etc. Among different enrichment approaches, hydrophilic interaction liquid chromatography (HILIC)-based magnetic separation has become one of the most popular methods in recent years, due to its high efficiency and selectivity for glycopeptide enrichment.. Herein, novel carboxymethyl-β-cyclodextrin (CMCD)-modified magnetic nanoparticles (MNPs) were synthesized via a carbodiimide activation method. CMCD was covalently bonded with the -OH group on the surface of MNPs through carbodiimide, and the proposed procedure provides a rapid and efficient alternative for glycopeptide enrichment due to its stable interaction, time-saving, and easy operation.. The prepared absorbents with a mean diameter of 15 nm demonstrated a strong magnetic response to an externally applied magnetic field. The results of thermogravimetric analysis showed the content of bound CMCD was 3 wt%. The outer CMCD layer conjugated on the Fe3 O4 core showed high hydrophilic surface property. In the analysis of a complex mouse liver sample, a total of 666 unique N-glycosylation sites corresponding to 494 glycosylated proteins were identified successfully.. The study demonstrated an easy-to-use CMCD-modified MNPs-based approach with high selectivity and high capacity in the enrichment of low-abundance glycopeptides from complex biological samples. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Animals; beta-Cyclodextrins; Carbodiimides; Glycopeptides; Liver; Magnetite Nanoparticles; Mass Spectrometry; Mice; Surface Properties

This finding described the electrochemical detection of tadalafil based on CM-β-cyclodextrin and SH-β-cyclodextrin functionalized Au@SiC nanohybrids film. The tadalafil electrochemical signal could be dramatically amplified by introducing 40% of acetonitrile in buffer medium and further enhanced by the host-guest molecular recognition capacity of β-cyclodextrin. Uniform and monodispersed ~5.0 nm Au NPs were anchored on the SiC-NH2 surface via a chemical reduction process by using polyethylene glycol and sodium citrate as dispersant and stabilizing agent. CM-β-CD was covalently bound on Au@SiC by combining the amine group of SiC-NH2 with the carboxyl group of CM-β-CD with the aid of EDC/NHS coupling agent. SH-β-CD could tightly attach to the surface of Au@SiC by the strong coordinating capability between Au and thiol. Differential pulse voltammetry was successfully used to quantify tadalafil within the concentration range of 0.01-100 µM under optimal conditions with a detection limit (S/N = 3) of 2.5 nM. In addition, the β-CD-Au@SiC nanohybrid electrochemical sensor showed high selectivity to two other erectile dysfunction drugs sildenafil and vardenafil. The proposed electrochemical sensing platform was successfully used to determine tadalafil in raw materials, herbal sexual health products, and spiked human serum samples.

Topics: Acetonitriles; beta-Cyclodextrins; Carbolines; Carbon Compounds, Inorganic; Electrochemical Techniques; Gold; Humans; Limit of Detection; Metal Nanoparticles; Phosphodiesterase 5 Inhibitors; Plants, Medicinal; Silicon Compounds; Tadalafil

A high-performance and selective adsorbent was developed for simultaneous extraction of 6 chlorobenzenes residues in soil samples by using magnetic solid phase extraction (MSPE) combined with automated SPE followed by gas chromatography-mass spectrometry (GC-MS). The adsorbent was synthesized by grafting carboxymethyl-β-cyclodextrin (CM-β-CD) on the surface of porous core-shell magnetic Fe3O4@flower like TiO2 microspheres (Fe3O4@fTiO2-CMCD), used as a carrier. The main factors (adsorbent amount, adsorption time, elution solvent, elution volume, and elution flow rate) affecting the extraction efficiency were investigated in detail. The adsorbent exhibited high loading capacity (25.6 mg g(-1) for 1,3-dichlorobenzene). This maybe due to meso-/macroporous TiO2 having high specific surface area; as a carrier of the β-cyclodextrin film, it could obviously increase the number of recognition sites. The newly developed adsorbent also showed good selectivity towards chlorobenzenes based on host-guest interactions between β-cyclodextrin (on adsorbent's surface) and targets, which can minimize complex matrix interference in soil samples. The proposed method was successfully applied for the analysis of environmental soil samples with recovery ranging from 87.3 to 104.3%. All target compounds showed good linearities with correlation coefficients (r) higher than 0.996. The limits of quantitation for the 6 CBs were 0.03-0.09 μg kg(-1). These findings confirmed meso-/macroporous structure Fe3O4@fTiO2-CMCD as a highly effective extraction material for use in trace CB analyses in complex soil samples.

Topics: Adsorption; beta-Cyclodextrins; Chlorobenzenes; Environmental Monitoring; Gas Chromatography-Mass Spectrometry; Magnetic Phenomena; Soil; Soil Pollutants; Solid Phase Extraction; Titanium

Non-porous C18 silica gel stationary phase (1 µm) was prepared and applied to chiral separation in pressurized capillary electrochromatography (pCEC) for the enantioseparation of various basic compounds. The non-porous silica particles (1 µm) were synthesized using modified St6ber method. C18 stationary phase (1 µm) was prepared by immobilization of chloro-dimethyl-octadecylsilane. Using carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral additive, the pCEC conditions including the content of acetonitrile (ACN), concentration of buffer, pH, the concentration of chiral additive and flow rate as well as applied voltage were investigated to obtain the optimal pCEC conditions for the separation of four basic chiral compounds. The column provided an efficiency of up to 190,000 plates/m. Bupropion hydrochloride, clenbuterol hydrochloride, metoprolol tartrate, and esmolol hydrochloride were baseline separated under the conditions of 5 mmol/L ammonium acetate buffer at pH 4. 0 with 20% (v/ v) acetonitrile, and 15 mmol/L CM-β-CD as the chiral additive. The applied voltage was 2 kV and flow rate was 0.03 mL/min with splitting ratio of 300:1. The resolution were 1.55, 2.82, 1. 69, 1. 70 for bupropion hydrochloride, clenbuterol hydrochloride, metoprolol tartrate, esmolol hydrochloride, respectively. The C18 coverage was improved by repeating silylation method. The synthesized 1 µm C18 packings have better mechanical strength and longer service life because of the special, non-porous structure. The column used in pCEC mode showed better separation of the racemates and a higher rate compared with those used in the capillary liquid chromatography (cLC) mode. This study provided an alternative way for the method of pCEC enantioseparation with chiral additives in the mobile phase and demonstrated the feasibility of micron particle stationary phase in chiral separation.

Topics: beta-Cyclodextrins; Bupropion; Capillary Electrochromatography; Chromatography, Liquid; Clenbuterol; Metoprolol; Propanolamines; Silanes; Silica Gel; Silicon Dioxide

In our work, the pH-controlled magnetic solid phase extraction for the determination of paraquat and diquat was introduced firstly. Furthermore, to clarify the mechanism of carboxymethyl-β-cyclodextrin functionalized magnetic adsorbents, we studied the pH-responsive supramolecular interaction between carboxymethyl-β-cyclodextrin (CM-β-CD) and paraquat/diquat by ultraviolet-visible (UV-vis) spectroscopy and nuclear magnetic resonance (NMR) experiment, and the energy-minimized structures were also obtained. Then, the functional group CM-β-CD was modified on the surface of magnetic materials to synthesize the adsorbent. The Fourier transform infrared spectrum (FT-IR) results proved the successful modification of CM-β-CD. Thus, this absorbent was applied for the determination of paraquat and diquat in water. Under the optimal condition, limits of detection (LODs) of paraquat and diquat were 0.8 μg L(-1) and 0.9 μg L(-1), relative standard deviations (RSD) and recoveries varied 0.7-4.6% and 86.5-106.6%, respectively. Good recoveries (70.2-100.0%) and low RSD (1.7-9.6%) were achieved in analyzing spiked water samples. Furthermore, with the capillary electrophoresis (CE) as the analyser, the whole analytical process did not need the attendance of organic solvents.

Topics: Adsorption; beta-Cyclodextrins; Herbicides; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Magnetics; Quaternary Ammonium Compounds; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

Carboxymethyl-β-cyclodextrin (CMβ-CD)-modified glycol chitosan (GCS) nanoparticles (GCS-CMβ-CD NPs) were synthesized, and their pH-sensitive drug-release properties were investigated. GCS-CMβ-CD NPs could encapsulate doxorubicin hydrochloride (DOX), and the encapsulation efficiency and loading capacity increased with the amount of CMβ-CD. Drug-release studies indicate that DOX released was greater in acidic medium (pH 5.0) than in weakly basic medium (pH 7.4). The mechanism underlying the pH-sensitive properties of the carrier was analyzed. Finally, the MCF-7 (human breast cancer) and SW480 cell lines (human colon cancer) were used to evaluate the cytotoxicity of the NPs. The drug-loaded carriers show good inhibition of the growth of cancer cells compared with free DOX, and the carriers have good biocompatibility. In addition, the drug-loaded NPs have sustained drug-release properties. All these properties of the newly synthesized GCS-CMβ-CD NPs suggest a promising potential as an effective anticancer drug-delivery system for controlled drug release.

Topics: Antineoplastic Agents; beta-Cyclodextrins; Cell Proliferation; Chitosan; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Drug Liberation; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Nanoparticles

A new capillary electrophoresis (CE) method using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector has been developed for the enantiomeric separation of meptazinol and its three intermediate enantiomers (intermediates II-IV), and validated for the application of quantitative determination of meptazinol in tablets. The primary factors affecting the separation efficiency, which include the chiral selector and its concentration, the buffer pH and composition, the organic modifiers used, and the applied voltage, were optimized. Baseline and satisfactory separations were obtained for meptazinol and its three intermediate enantiomers. For quantitative analysis of meptazinol, the method was performed at the condition using 2.0 mmol/L CM-β-CD in 20 mmol/L H3 PO4 buffer adjusted to a pH of 6.00 with an applied voltage of 15 kV and containing 5% acetonitrile. After validation of the method in terms of its linearity, limits of detection and quantitation, accuracy, precision and selectivity, the method was successfully applied to the quantitation of meptazinol in pharmaceutical formulations.

Topics: Adsorption; beta-Cyclodextrins; Chemistry, Pharmaceutical; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Meptazinol; Stereoisomerism

A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation was achieved on an uncoated 40.2 cm×75 μM fused silica capillary with an applied voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate-25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-β-cyclodextrin. The detection wavelength was 200 nm. Under these optimized conditions, satisfactory chiral separations of four pair enantiomers were achieved in less than 7 min in vitro. After one step clean-up liquid-liquid extraction using 96-well format, sample was introduced capillary zone electrophoresis with acetonitrile-field-amplified sample stacking to enhance the sensitivity of enantiomers. The method was validated with respect to specificity, linearity, lower limit of quantitation, accuracy, precision, extraction recovery and stability. The lower limit of quantification was 0.5 ng/mL with linear response over the 0.5-50 ng/mL concentration range for each mirtazapine, N-demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and validated method has been successfully applied to the enantioselective pharmacokinetic studies in 12 healthy volunteers after oral administration of rac- mirtazapine.

Topics: Acetonitriles; Administration, Oral; Antidepressive Agents, Tricyclic; beta-Cyclodextrins; Biotransformation; Buffers; Chemical Fractionation; Cyclic N-Oxides; Electrophoresis, Capillary; Humans; Limit of Detection; Male; Mianserin; Mirtazapine; Reproducibility of Results; Stereoisomerism

An innovative ex situ soil washing technology was developed in this study to remediate organochlorine pesticides (OCPs) and heavy metals in a mixed contaminated site. Elevated temperature (60 °C) combined with ultrasonication (40 kHz, 20 min) at 50 mL L(-1) maize oil and 45 g L(-1) carboxylmethyl-β-cyclodextrin were effective in extracting pollutants from the soil. After two successive washing cycles, the removal efficiency rates for total OCPs, mirex, endosulfans, chlordanes, Cd, and Pb were approximately 94.7%, 87.2%, 98.5%, 92.3%, 91.6%, and 87.3%, respectively. Cultivation of vetiver grass and addition of nutrients for 3 months further degraded 34.7% of the residual total OCPs and partially restored the microbiological functions of the soil. This result was indicated by the significant increase in the number, biomass C, N, and functioning diversity of soil microorganisms (p < 0.05). After the treatment, the residual OCPs and heavy metals existed as very slowly desorbing fraction and residual fraction, as evaluated by Tenax extraction combined with a first-three-compartment model and sequential extraction. Moreover, the secondary environmental risk of residual pollutants in the remediated soil was at an acceptable level. The proposed combined cleanup strategy proved to be effective and environmentally friendly.

Topics: beta-Cyclodextrins; Cadmium; Chrysopogon; Corn Oil; Environmental Restoration and Remediation; Hydrocarbons, Chlorinated; Lead; Pesticides; Soil; Soil Pollutants; Sonication

Novel organic-inorganic hybrid ultrathin films were fabricated by alternate assembly of cationic exfoliated Mg-Al-layered double hydroxide (LDH) nanosheets and carboxymethyl-β-cyclodextrin (CMCD) as a polyanion onto a glassy carbon electrode (GCE) via a layer-by-layer (LBL) approach. The multilayer films were then characterized by means of X-ray powder diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM). These films were found to possess a long range stacking order in the normal direction of the substrate with a continuous and uniform morphology. Its electrochemical performance was systematically investigated. Our results demonstrate that such a newly designed (LDH/CMCD)n multilayer film, combining the individual properties of CMCD (a high supramolecule recognition and enrichment capability) together with LDH nanosheets (a rigid inorganic matrix), can be applied to a sensitive, simple, and label-free capacitive detection of acephatemet (AM). Molecular docking calculations further disclose that the selective sensing behavior toward AM may be attributed to the specific binding ability of CMCD to AM. Under the optimized conditions, the capacitive change of AM was proportional to its concentration ranging from 0.001 to 0.10 μg mL(-1) and 0.1 to 0.8 μg mL(-1) with a detection limit 0.6 ng mL(-1) (S/N=3). Toward the goal for practical applications, this simple probe was further evaluated by monitoring AM in real samples.

Topics: beta-Cyclodextrins; Electrochemical Techniques; Electrodes; Hydroxides; Limit of Detection; Molecular Docking Simulation; Nanostructures; Organophosphates; Pesticides; X-Ray Diffraction

Cyclodextrins (CDs) are typically functionalized to increase their solubility or provide reactive functional groups suitable for grafting onto polymer supports designed for controlled release applications. In this work, a systematic investigation was performed on the binding behaviour of the model drug dexamethasone with βCD derivatives functionalized with a small, negatively charged moiety (carboxyl groups, CM) and a large, neutral, reactive moiety (hydrazide groups, Hzd), both free and grafted to dextran. Solubilization capacities and thermodynamic parameters were examined through phase solubility analysis, the method of continuous variation, and isothermal titration calorimetry. Alternate mechanisms of solubilization were also investigated by probing aggregation of both free and complexed βCD derivatives using nanoparticle tracking analysis. CM/βCD and Hzd/βCD derivatives exhibited similar complexation behaviours with dexamethasone: 1:1 stoichiometry, linear phase solubility profiles, and consistent binding enthalpies. Increased functionalization reduced the complex stability constant as well as the complexation efficiency, while polymer grafting resulted in no significant change in binding properties. CM/βCD derivatives complexed with dexamethasone formed more and larger aggregates, while Hzd/βCD derivatives formed significantly fewer, smaller aggregates and dextran-grafted βCD did not aggregate. Such characterization of βCD derivatives provides a framework for designing βCDs as pharmaceutical excipients or drug binding sites in drug delivery vehicles.

Topics: Adipates; beta-Cyclodextrins; Dexamethasone; Hydrophobic and Hydrophilic Interactions; Particle Size; Solubility

Polycyclic aromatic hydrocarbons (PAHs)/heavy metals/fluorine (F) mixed-contaminated sites caused by abandoned metallurgic plants are receiving wide attention. To address the associated environmental problems, this study was initiated to investigate the feasibility of using carboxymethyl-β-cyclodextrin (CMCD) and carboxymethyl chitosan (CMC) solution to enhance ex situ soil washing for extracting mixed contaminants. Further, Tenax extraction method was combined with a first-three-compartment model to evaluate the environmental risk of residual PAHs in washed soil. In addition, the redistribution of heavy metals/F after decontamination was also estimated using a sequential extraction procedure. Three successive washing cycles using 50 g/L CMCD and 5 g/L CMC solution were effective to remove 94.3% of total PAHs, 93.2% of Pb, 85.8% of Cd, 93.4% of Cr, 83.2% of Ni and 97.3% of F simultaneously. After the 3rd washing, the residual PAHs mainly existed as very slowly desorbing fractions, which were in the form of well-aged, well-sequestered compounds; while the remaining Pb, Cd, Cr, Ni and F mainly existed as Fe-Mn oxide and residual fractions, which were always present in stable mineral forms or bound to non-labile soil fractions. Therefore, this combined cleanup strategy proved to be effective and environmentally friendly.

Topics: beta-Cyclodextrins; Chitosan; Fluorine; Metallurgy; Metals, Heavy; Polycyclic Aromatic Hydrocarbons; Soil; Soil Pollutants

Currently, clinical operation treatments, chemotherapy and radiotherapy just could eliminate local tumor cells. However, chemotherapy and radiotherapy also injury normal cells and lead to serious side effects and toxicities. So, it is necessary to find an effective target cancer carrier that delivers the anticancer agents into tumor cells and reduces normal cells' injury. Folic acid (FA) is a classical targeting agent mediates internalization of chemical drugs into tumor cells which over-express folate receptor (FR) on their surface. We herein report that based on host-guest interaction, NPs decorated by novel folate enhance antitumor drug delivery. BSA-NPs were prepared by desolvation method and carboxymethyl-β-cyclodextrin (CM-β-CD) was conjugated to the surface of NPs by carbodiimide coupling to hold FA. From in vitro cytotoxicity assay, cell apoptosis study, intracellular ATP level assay and western blot, we can see that FA-CM-β-CD-BSA NPs as good monodispersity, negative charge, and homogenous particle size have a high encapsulation efficiency. The results showed that MTT and cell apoptosis demonstrated that FA-decorated NPs exhibit stronger inhibition rate and induce obvious apoptosis in FR positive Hela cells as compared to free drug and FA undecorated NPs. Moreover, 5-fluorouracil (5-Fu) loaded FA-CM-β-CD-BSA NPs down-regulate ATP levels and increase the expression of caspase-3. Taken together, FA-CM-β-CD-BSA NPs enhance FR receptor-mediated endocytosis and lead to more intracellular uptake of drug, inducing the higher apoptosis ratio of cells than free 5-Fu.

Topics: Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Screening Assays, Antitumor; Endocytosis; Female; Folate Receptors, GPI-Anchored; Folic Acid; HeLa Cells; Humans; Models, Molecular; Molecular Structure; Nanoparticles; Particle Size; Rhodamines; Structure-Activity Relationship; Surface Properties; Tumor Cells, Cultured; Uterine Cervical Neoplasms

In this study, we developed a magnetically multifunctional purifying material for efficient removal of matrix interferences, especially certain organochlorine pesticide (DDT, DDE, and DDD), during the determination of toxic highly chlorinated polychlorinated biphenyls (PCBs) at trace levels in soil samples. The multifunctional adsorbent (CMCD-NH2-MNPs) was prepared by grafting carboxymethyl-β-cyclodextrin on the surface of amino-functionalized magnetite (Fe3O4) nanoparticles. CMCD-NH2-MNPs has stronger host-guest complexation with DDT, DDE, and DDD, but the same adsorbent shows weaker adsorption ability toward highly chlorinated PCBs (from tetra- to octa-chlorinated PCBs) owing to their steric hindrance effect. Based on this principle, a simple and rapid gas chromatography-mass spectrometry (GC-MS) method was developed for six indicator PCBs (PCB28, PCB52, PCB101, PCB138, PCB153, and PCB180) in soil. Comparative studies were conducted to determine the clean-up efficiency of the following three techniques: (i) Oasis-HLB, (ii) multi-layer silica column, and (iii) dSPE employing CMCD-NH2-MNPs. The results indicate that CMCD-NH2-MNPs as the purification material can easily and effectively remove DDT, DDE, and DDD in soil samples within a short duration of time. The recoveries for highly chlorinated PCBs were in the range of 85.4-102.2%, with RSDs varying between 1.0 and 6.5%. The proposed method was verified as one of the most effective clean-up procedures for the analysis of highly chlorinated PCBs in real soil samples.

Topics: Adsorption; beta-Cyclodextrins; Gas Chromatography-Mass Spectrometry; Magnetite Nanoparticles; Pesticides; Polychlorinated Biphenyls; Soil; Soil Pollutants

A rapid capillary electrophoresis method using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector was developed and validated for the enantiomeric purity determination of levamlodipine besylate bulk drug. Several parameters for were optimized for a satisfactory enantioresolution, including pH of background electrolyte, the concentration of chiral selector, buffer concentration, capillary temperature and voltage. The highest resolution (Rs = 9.8) was obtained with 4 mM CM-β-CD dissolved in 40 mM phosphate buffer (pH 3.5), at temperature 25 °C and voltage 30 kV, normal polarity. This method was fully validated for the enantiomeric purity determination of the R-amlodipine at the 0.2 % level. The established method was validated in terms of selectivity, LOD and LOQ (0.001 and 0.003 mg mL(-1)), linearity (y = 2.8943x + 0.1386, r (2) = 0.9991), precision and accuracy (95-104 %). Finally, the method was further applied to investigate the enantiomeric purity of levamlodipine in bulk samples.

Topics: beta-Cyclodextrins; Electricity; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Niacin; Osmolar Concentration; Stereoisomerism; Temperature

Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells.. We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of -18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs.. These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Autophagy; beta-Cyclodextrins; Cell Survival; Drug Delivery Systems; Folate Receptors, GPI-Anchored; Folic Acid; Gefitinib; HeLa Cells; Humans; Molecular Targeted Therapy; Nanoparticles; Quinazolines; Serum Albumin, Bovine; Spectroscopy, Fourier Transform Infrared

Efficient target delivery system for insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. Herein, glycol chitosan-carboxymethyl β-cyclodextrins (G-chitosan-CM-dextrins) was synthesized for delivering different hydrophobic anticancer drugs. Surface plasmon resonance and UV-vis spectroscopy results showed that all the three anticancer drugs (5-fluorouracil, doxorubicin, and vinblastine) could be successfully loaded into the cavities of the covalently linked CM-dextrins. Moreover, the free carboxymethyl groups could enhance the binding interactions between the covalently linked CM-dextrins and anticancer drugs. Release behaviors with pH changes of the three drugs were also explored, result showed different drugs would be released by different ways, as for doxorubicin, pH sensitive release has been realized. The obtained G-chitosan-CM-dextrins carrier has both mucoadhesive property of G-chitosan and hydrophobic cavities of β-cyclodextrins. Therefore, the new synthesized G-chitosan-CM-dextrins carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy.

Topics: Antineoplastic Agents; beta-Cyclodextrins; Chitosan; Doxorubicin; Drug Carriers; Fluorouracil; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface Plasmon Resonance; Vinblastine

A green and environment-friendly method for synthesis of water-soluble and fluorescent Ag nanoclusters was developed using carboxymethyl-β-cyclodextrin (CM-β-CD) as both reducing and stabilizing reagent. The optical properties of Ag nanoclusters were characterized using the photoluminescence, ultraviolet-visible absorption, and laser desorption time of flight mass spectroscopies. The role of carboxylic groups was discussed in the photoactivated synthesis of Ag nanoclusters. Increasing the substitute of carboxylic groups on CM-β-CD was propitious to the formation of Ag nanoclusters and the stability of the produced silver nanoclusters was greatly improved. The in vitro antimicrobial ability of the produced Ag nanoclusters was tested. Compared with a silver nitrate solution and a typical Ag colloid, Ag nanoclusters stabilized by CM-β-CD exhibited greatly strong antimicrobial ability.

Topics: Anti-Infective Agents; beta-Cyclodextrins; Escherichia coli; Fluorescent Dyes; Hydrogen-Ion Concentration; Metal Nanoparticles; Silver

A capillary electrophoretic method has been established for the separation of the enantiomers of clenbuterol. The effects of pH value, composition of the background electrolyte, concentration of carboxymethyl-β-cyclodextrin (CM-β-CD), capillary temperature and running voltage have been investigated. The two enantiomers were separated in an uncoated capillary with phosphate buffer (50 mmol/L, pH 3.5) containing 10 mmol/L CM-β-CD. The capillary temperature was at 15°C and applied voltage was at 20 kV. The inclusion complex of CM-β-CD and clenbuterol was synthesized and characterized by two-dimensional rotating frame spectroscopy (2D ROESY). Based on the 2D ROESY analysis, an inclusion structure of the clenbuterol/CM-β-CD complex was proposed, in which clenbuterol penetrated CM-β-CD in a tilted manner due to the interaction of intermolecular hydrogen bonds between clenbuterol and CM-β-CD.

Topics: beta-Cyclodextrins; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Clenbuterol; Electrophoresis, Capillary; Limit of Detection; Linear Models; Magnetic Resonance Spectroscopy; Reproducibility of Results; Stereoisomerism

The enantioseparation of acidic and neutral compounds can be successfully achieved in capillary electrophoresis (CE) using dual cyclodextrin (CD) systems. This chapter describes how to separate the enantiomers of acidic or neutral substances using dual CD systems made up of a negatively charged CD derivative, i.e., sulfobutyl-β-CD (SB-β-CD) or carboxymethyl-β-CD (CM-β-CD), in combination with a neutral one, namely, heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD). An acidic compound (carprofen) and a weakly acidic drug (pentobarbital) were selected as model compounds.

Topics: beta-Cyclodextrins; Carbazoles; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Models, Theoretical; Pentobarbital; Stereoisomerism

Chiral resolution aromatic amino acids, DL-tryptophan (DL-Trp), DL-phenylalanine (DL-Phe), DL-tyrosine (DL-Tyr) from phosphate buffer solution was achieved in present study employing the concept of selective adsorption by surface functionalized magnetic nanoparticles (MNPs). Surfaces of magnetic nanoparticles were functionalized with silica and carboxymethyl-β-cyclodextrin (CMCD) to investigate their adsorption resolution characteristics. Resolution of enantiomers from racemic mixture was quantified in terms of enantiomeric excess using chromatographic method. The MNPs selectively adsorbed L-enantiomers of DL-Trp, DL-Phe, and DL-Tyr from racemic mixture and enantiomeric excesses (e.e.) were determined as 94%, 73% and 58%, respectively. FTIR studies demonstrated that hydrophobic portion of enantiomer penetrated into hydrophobic cavity of cyclodextrin molecules to form inclusion complex. Furthermore, adsorption site was explored using XPS and it was revealed that amino group at chiral center of the amino acid molecule formed hydrogen bond with secondary hydroxyl group of CMCD molecule and favorability of hydrogen bond formation resulted in selective adsorption of L-enantiomer. Finally, stability constant (K) and Gibbs free energy change (-ΔG°) for inclusion complexation of CMCD with L-/D-enantiomers of amino acids were determined using spectroflurometry in aqueous buffer solution. Higher binding constants were obtained for inclusion complexation of CMCD with L-enantiomers compared to D-enantiomers which stimulated enantioselective properties of CMCD functionalized magnetite silica nanoparticles.

Topics: Adsorption; Amino Acids, Aromatic; beta-Cyclodextrins; Hydrogen Bonding; Magnetite Nanoparticles; Photoelectron Spectroscopy; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared; Stereoisomerism

A new nanomedicine consisting of chitosan/carboxymethyl-β-cyclodextrin loaded with unfractioned or low-molecular-weight heparin is described and its potential in asthma treatment is evaluated. The nanoparticles are prepared by ionotropic gelation showing a size that between 221 and 729 nm with a positive zeta potential. The drug association efficiency is higher than 70%. Developed nanosystems are stable in Hank's balanced salt solution at pH = 6.4, releasing the drug slowly. Ex vivo assays show that nanocarriers lead to an improvement of heparin preventing mast cell degranulation. These results agree with the effective cellular internalization of the fluorescently labeled nanocarriers, and suggest these nanomedicines as promising formulations for asthma treatment.

Topics: Animals; Asthma; beta-Cyclodextrins; Cell Degranulation; Cell Survival; Chitosan; Drug Carriers; Drug Compounding; Female; Heparin, Low-Molecular-Weight; Histamine; Histamine Release; Humans; Mast Cells; Molecular Weight; Nanomedicine; Particle Size; Rats; Rats, Sprague-Dawley; Spectrometry, Fluorescence

CE methods with capacitively coupled contactless conductivity detection (C(4)D) were developed for the enantiomeric separation of the following stimulants: amphetamine (AP), methamphetamine (MA), ephedrine (EP), pseudoephedrine (PE), norephedrine (NE) and norpseudoephedrine (NPE). Acetic acid (pH 2.5 and 2.8) was found to be the optimal background electrolyte for the CE-C(4)D system. The chiral selectors, carboxymethyl-β-cyclodextrin (CMBCD), heptakis(2,6-di-O-methyl)-β-cyclodextrin (DMBCD) and chiral crown ether (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18C6H(4)), were investigated for their enantioseparation properties in the BGE. The use of either a single or a combination of two chiral selectors was chosen to obtain optimal condition of enantiomeric selectivity. Enantiomeric separation of AP and MA was achieved using the single chiral selector CMBCD and (hydroxypropyl)methyl cellulose (HPMC) as the modifier. A combination of the two chiral selectors, CMBCD and DMBCD and HPMC as the modifier, was required for enantiomeric separation of EP and PE. In addition, a combination of DMBCD and 18C6H(4) was successfully applied for the enantiomeric separation of NE and NPE. The detection limits of the enantiomers were found to be in the range of 2.3-5.7 μmol/L. Good precisions of migration time and peak area were obtained. The developed CE-C(4)D method was successfully applied to urine samples of athletes for the identification of enantiomers of the detected stimulants.

Topics: Acetic Acid; Amphetamines; beta-Cyclodextrins; Central Nervous System Stimulants; Crown Ethers; Electric Conductivity; Electrophoresis, Capillary; Humans; Limit of Detection; Propanolamines; Reproducibility of Results; Stereoisomerism

A novel magnetic nanoadsorbent (CMCD-APTS-MNPs) containing the superparamagnetic and molecular recognition properties was synthesized by grafting carboxymethyl-β-cyclodextrin (CM-β-CD) on 3-aminopropyltriethoxysile (APTS) modified Fe(3)O(4) nanoparticles. The feasibility of using CMCD-APTS-MNPs as magnetic nanoadsorbent for selective adsorption of adenosine (A) and guanosine (G) based on inclusion and molecular recognition was demonstrated. The as-synthesized magnetic nanoparticles were characterized by TEM, FTIR and TGA analyses. The effects of pH and initial nucleoside concentrations on the adsorption behavior were studied. The complexation of CMCD-APTS-MNPs with both nucleosides was found to follow the Langmuir adsorption isotherm. The CMCD-APTS-MNPs showed a higher adsorption ability and selectivity for G than A under identical experimental conditions, which results from the ability of selective binding and recognition of the immobilized CM-β-CD towards G. The driving force of the separation between G and A is through the different weak interaction with grafted CM-β-CD, i.e., hydrogen bond interaction, which is evidenced by different inclusion equilibrium constants and FTIR analyses of inclusion complexes between grafted cyclodextrin and the guest molecules. Our results indicated that this nanoadsorbent would be a promising tool for easy, fast and selective separation, analysis of nucleosides and nucleotides in biological samples.

Topics: Adsorption; beta-Cyclodextrins; Hydrogen-Ion Concentration; Kinetics; Magnetite Nanoparticles; Nucleosides; Propylamines; Recycling; Silanes; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Thermogravimetry

Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the -OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.

Topics: Adrenergic Antagonists; beta-Cyclodextrins; Binding Sites; Buffers; Cyclodextrins; Electrophoresis, Capillary; Hydrogen Bonding; Hydrogen-Ion Concentration; Molecular Conformation; Molecular Docking Simulation; Stereoisomerism; Temperature; Thermodynamics

Glucose and cell swelling induce insulin secretion by alternative signaling pathways. Swelling-induced secretion is in most systems independent of calcium and various mediators of glucose stimulation. Comparison of two insulinoma tumor cell lines revealed surprising difference; INS-1E cells in contrast to INS-1 cells and isolated rat pancreatic islets do not respond to hypotonicity in the presence of calcium. To delineate the role of cholesterol the effect of its extraction or addition on the insulin secretion in response to glucose and cell swelling was compared. INS-1E cells have significantly higher cholesterol content than INS-1 cells (58.5 ± 2.9 and 46.3 ± 2.5 mg chol/mg prot respectively). After cholesterol desorption by 1.0, 5.0 and 10.0 mM of carboxymethyl-β-cyclodextrin, methyl-β-cyclodextrin, or 2-hydroxypropyl-β- cyclodextrin the response to hypotonicity in INS-1E cells emerged. On the contrary, supplementation of INS-1 cells with cholesterol inhibited their response to cell swelling. Cyclodextrin pretreatment inhibited glucose-induced insulin secretion from INS-1 cells while INS-1E cells were more resistant to their effect.. Cellular cholesterol content substantially affects secretory process; both high and low levels could be inhibitory. Absence of swelling-induced insulin secretion in INS-1E cells despite adequate response to glucose is related to their high cholesterol content. Optimal cholesterol concentration is different for either type of stimulation; swelling-induced mechanism is more sensitive to higher cholesterol content. The difference is likely to reflect involvement of sequential type exocytosis after cell swelling. Sensitivity of secretory processes suggests that either hypercholesterolemia or excessive effort to decrease plasma cholesterol in patients could have adverse effect on insulin secretion.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Cell Line, Tumor; Cholesterol; Dose-Response Relationship, Drug; Insulin; Insulin Secretion; Insulin-Secreting Cells; Rats

Capillary electrophoresis (CE) methods for chiral resolution of five antimalarial drugs (primaquine, tafenoquine, mefloquine, chloroquine and quinacrine) were developed by using a wide selection of neutral and anionic cyclodextrin (CD) derivatives. The use of sulfobutyl-β-CD and carboxymethyl-β-CD (CMBCD) resulted in good resolution of quinacrine and tafenoquine, respectively. New results are presented for resolutions of chloroquine and mefloquine. Application of carboxyalkyl- and sulfobutyl-CD derivatives provided improved resolution for primaquine. The impurity in primaquine sample detected by CE was identified as quinocide by MS and NMR. CMBCD provided not only the best separation of primaquine from quinocide but also the simultaneous complete resolution of both compounds.

Topics: Aminoquinolines; Anions; Antimalarials; beta-Cyclodextrins; Chloroquine; Cyclodextrins; Electrophoresis, Capillary; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mefloquine; Primaquine; Stereoisomerism

A novel nano-adsorbent, carboxymethyl-β-cyclodextrin modified Fe(3)O(4) nanoparticles (CMCD-MNPs) is fabricated for removal of copper ions from aqueous solution by grafting CM-β-CD onto the magnetite surface via carbodiimide method. The characteristics results of FTIR, TEM, TGA and XPS show that CM-β-CD is grafted onto Fe(3)O(4) nanoparticles. The grafted CM-β-CD on the Fe(3)O(4) nanoparticles contributes to an enhancement of the adsorption capacity because of the strong abilities of the multiple hydroxyl and carboxyl groups in CM-β-CD to adsorb metal ions. The adsorption of Cu(2+) onto CMCD-MNPs is found to be dependent on pH and temperature. Adsorption equilibrium is achieved in 30 min and the adsorption kinetics of Cu(2+) is found to follow a pseudo-second-order kinetic model. Equilibrium data for Cu(2+) adsorption are fitted well by Langmuir isotherm model. The maximum adsorption capacity for Cu(2+) ions is estimated to be 47.2mg/g at 25 °C. Furthermore, thermodynamic parameters reveal the feasibility, spontaneity and exothermic nature of the adsorption process. FTIR and XPS reveal that Cu(2+) adsorption onto CMCD-MNPs mainly involves the oxygen atoms in CM-β-CD to form surface-complexes. In addition, the copper ions can be desorbed from CMCD-MNPs by citric acid solution with 96.2% desorption efficiency and the CMCD-MNPs exhibit good recyclability.

Topics: Adsorption; beta-Cyclodextrins; Copper; Kinetics; Magnetics; Microscopy, Electron, Transmission; Nanoparticles; Spectroscopy, Fourier Transform Infrared; Thermogravimetry

Surface of magnetic silica nanoparticles is modified by grafting with carboxymethyl-β-cyclodextrin (CM-β-CD) via carbodiimide activation. The functionalized magnetic core-shell nanoparticles (MNPs) are characterized by Transmission Electron Microscopy (TEM), Fourier Transform Infra Red (FTIR) spectroscopy, X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS) and Vibrating Sample Magnetometer (VSM). These nano-sized particles are scrutinized for adsorption of certain chiral aromatic amino acid enantiomers namely, d- and l-tryptophan (Trp), d- and l-phenylalanine (Phe) and d- and l-tyrosine (Tyr) from phosphate buffer solutions. Adsorption capacities of the coated magnetic nanoparticles toward amino acid enantiomers are in the order: l-Trp>l-Phe>l-Tyr and under the same condition, adsorption capacities are higher for l-enantiomers than the corresponding d-enantiomers. All the equilibrium adsorption isotherms are fitted well to Freundlich model. FTIR studies depict significant changes after adsorption of amino acids onto nanoparticles. The stretching vibration frequencies of NH bonds of the amino acid molecules are changed with complex formation through host-guest interaction. The structure and hydrophobicity of amino acid molecules emphasize the interactions between amino acid molecules and the nano-adsorbents bearing cyclodextrin, thus play important roles in the difference of their adsorption behaviors.

Topics: Adsorption; Amino Acids, Aromatic; beta-Cyclodextrins; Ferrosoferric Oxide; Magnetics; Nanoparticles; Silicon Dioxide; Surface Properties

Hazardous waste sites are commonly contaminated with both organic and metal pollutants. Many metal pollutants have been shown to inhibit organic pollutant biodegradation. We investigated the ability of a modified, polydentate cyclodextrin (carboxymethyl-beta-cyclodextrin, CMCD) to reduce the toxicity of 33.4 microM cadmium, cobalt or copper during naphthalene degradation by a Burkholderia sp. in 120 h aerobic, batch studies. The highest investigated concentration of CMCD, 3340 microM, reduced cadmium, cobalt, and copper toxicity. With each metal, the length of the lag phase was reduced (by as much as 108 h with cobalt or copper), the cell yield was increased (by as much as a factor of 16 with cobalt), and the growth rate was increased (by as much as a factor of 31 with cobalt). The degrader was unable to use CMCD as the sole source of carbon and energy. Our data suggest that the ability of CMCD to complex metals plays an important role in its ability to mitigate metal toxicity and that CMCD has the potential to enhance biodegradation in organic and metal co-contaminated environments.

Topics: Analysis of Variance; beta-Cyclodextrins; Biodegradation, Environmental; Bioreactors; Burkholderia; Cadmium; Cobalt; Copper; Environmental Pollution; Naphthalenes; Time Factors

A novel adsorbent of carboxymethyl-beta-cyclodextrin modified nanometer TiO(2) (CM-beta-CD/TiO(2)) was prepared and used as a solid-phase extraction (SPE) material coupled to fluorescence spectroscopy determination of l-tryptophan (l-Trp) in biological samples. The experimental conditions for modified nanometer TiO(2) separation/preconcentration of l-Trp were optimized. The adsorption capacity of CM-beta-CD/TiO(2) for l-Trp was 75.2 microg/g. The linear range, detection limit (DL), and the relative standard deviation (RSD) were 0.10-1.20 microg/mL, 18.8 ng/mL, and 0.67% (n=3, 1.0 microg/mL), respectively, with a preconcentration factor of 10. The developed method was applied to determination of l-Trp in real samples and the recoveries were found to be in the range of 99.2-100.3%. For validation, a comparison material of NIC-140686 sample was analyzed and the determined value was in good agreement with the certified value.

Topics: Adsorption; beta-Cyclodextrins; Limit of Detection; Solid Phase Extraction; Spectrometry, Fluorescence; Titanium; Triticum; Tryptophan

The objective of the present study was to evaluate the potential influence of carboxymethyl-beta-cyclodextrin (CM-beta-CyD) on the aqueous solubility, chemical stability and oral bioavailability of famotidine (FMT) as well as on its bitter taste. We examined the effect of the CM-beta-CyD on the acidic degradation of FMT compared with that for sulfobutyl-ether-beta-cyclodextrin (SBE-beta-CyD). The potential use of CM-beta-CyD for orally disintegrating tablets (ODTs) was evaluated in vitro and in vivo. A taste perception study was also carried out. A strong stabilizing influence of CM-beta-CyD was observed against the acidic degradation, in sharp contrast to SBE-beta-CyD which induced a weird destabilizing effect on FMT. (13)C NMR was used to investigate the interaction mode between FMT and the 2 CyDs. In vivo study of ODTs indicated a significant increase in C(max), AUC and oral bioavailability in the case of FMT-CM-beta-CyD tablets, compared with plain drug tablets. However, no significant difference in T(max) and t(1/2) was observed. CM-beta-CyD complexation appears to be an acceptable strategy for enhancing the oral bioavailability of FMT owing to its dramatic effect on the aqueous solubility and chemical stability of the drug. In addition, it has a pronounced effect on masking the bitter taste of FMT.

Topics: Administration, Oral; Adult; Animals; Anti-Ulcer Agents; Area Under Curve; beta-Cyclodextrins; Biological Availability; Drug Stability; Famotidine; Female; Half-Life; Humans; Intestinal Absorption; Male; Rats; Rats, Wistar; Solubility; Tablets; Taste; Young Adult

An improved approach for the surface modification of poly(dimethylsiloxane) (PDMS) using carboxymethyl cellulose (CMC), carboxymethyl beta-1,3-dextran (CMD), and alginic acid (AA) was investigated. The PDMS substrates were first oxidized in a H(2)SO(4)/H(2)O(2) solution to transform the Si-CH(3) groups on their surfaces into Si-OH groups. Then methacrylate groups were grafted onto the substrates through a silanization reaction using 3-(trimethoxysilyl)propyl methacrylate. Sequentially, cysteamine was conjugated onto the silanized surfaces by the reaction between the thiol and methacrylate groups under 254 nm UV exposure. Afterward, the amino-terminated PDMS substrates were sequentially reacted with CMC, CMD, and AA in the presence of N-hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, resulting in the grafting of polysaccharides onto PDMS surfaces. The composition and chemical state of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS). In addition, the stability and dynamic characteristics of the polysaccharide-grafted PDMS substrates were investigated by XPS and temporal contact angle experiments. A protein adsorption assay using bovine serum albumin (BSA), chicken egg albumin, lysozyme, and RNase-A showed that the introduction of CMD and AA can reduce the adsorption of negatively charged BSA and chicken egg albumin, but increase the adsorption of the positively charged lysozyme and RNase-A. However, CMC-modified PDMS surfaces showed protein-repelling properties, regardless of whether the protein was positively or negatively charged. A cell culture and migration study of glioma C6, MKN-45, MCF-7, and HepG-2 cells revealed that the polysaccharide-modified PDMS greatly improved the cytocompatibility of native PDMS.

Topics: Adsorption; Alginates; Animals; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Cattle; Cell Line, Tumor; Dimethylpolysiloxanes; Glucuronic Acid; Hexuronic Acids; Humans; Methacrylates; Muramidase; Organosilicon Compounds; Photoelectron Spectroscopy; Polysaccharides; Proteins; Ribonuclease, Pancreatic; Serum Albumin, Bovine; Surface Properties

A rapid and effective method was developed for the chiral separation of raltitrexed (RD) enantiomers by carboxymethyl-beta-cyclodextrin (CM-beta-CD)-modified micellar electrokinetic chromatography (MEKC). Optimization of conditions including the type and concentration of the chiral selector, concentration of sodium dodecyl sulfate (SDS), pH and concentration of the background electrolyte (BGE), capillary temperature, and applied voltage was investigated. The enantiomers of raltitrexed could be separated with satisfactory resolution and linear response by using 75 mM Tris-phosphate at pH 8.0 containing 30 mM SDS and 8 mM CM-beta-CD as buffer system. Furthermore, the usefulness of this method was demonstrated in a purity test of a real synthetic drug sample.

Topics: beta-Cyclodextrins; Chromatography, Micellar Electrokinetic Capillary; Electrochemistry; Electrolytes; Hydrogen-Ion Concentration; Molecular Conformation; Quinazolines; Sodium Dodecyl Sulfate; Stereoisomerism; Temperature; Thiophenes; Time Factors

Carboxymethyl-beta-cyclodextrin (CMCD) has been suggested as a complexing agent for remediation of sites co-contaminated with metals and organic pollutants. As part of an attempt to construct a geochemical complexation model for metal-CMCD interactions, conditional formation constants for the complexes between CMCD and 7 metal ions (Ba, Ca, Cd, Ni, Pb, Sr, and Zn) are estimated from experimental data. Stable metal concentrations were reached after approximately 1 day and estimated logarithmic conditional formation constants range from -3.2 to -5.1 with confidence intervals within +/-0.08 log units. Experiments performed at 10 degrees C and 25 degrees C show that temperature affects the solubility of the metal salts but the strength of CMCD-metal complexes are not affected by this temperature variation. The conditional stability constants and complexation model presented in this work can be used to screen CMCD as a potential remediation agent for clean-up of contaminated soil and groundwater.

Topics: beta-Cyclodextrins; Environmental Pollution; Metals; Solubility; Surface-Active Agents

An experimental design optimization (Box-Behnken design, BBD) was used to develop a CE method for the simultaneous resolution of propranolol (Prop) and 4-hydroxypropranolol enantiomers and acetaminophen (internal standard). The method was optimized using an uncoated fused silica capillary, carboxymethyl-beta-cyclodextrin (CM-beta-CD) as chiral selector and triethylamine/phosphoric acid buffer in alkaline conditions. A BBD for four factors was selected to observe the effects of buffer electrolyte concentration, pH, CM-beta-CD concentration and voltage on separation responses. Each factor was studied at three levels: high, central and low, and three center points were added. The buffer electrolyte concentration ranged from 25 to 75 mM, the pH ranged from 8 to 9, the CM-beta-CD concentration ranged from 3.5 to 4.5% w/v, and the applied run voltage ranged from 14 to 20 kV. The responses evaluated were resolution and migration time for the last peak. The obtained responses were processed by Minitab to evaluate the significance of the effects and to find the optimum analysis conditions. The best results were obtained using 4% w/v CM-beta-CD in 25 mM triethylamine/H3PO4 buffer at pH 9 as running electrolyte and 17 kV of voltage. Resolution values of 1.98 and 1.95 were obtained for Prop and 4-hydroxypropranolol enantiomers, respectively. The total analysis time was around of 15 min. The BBD showed to be an adequate design for the development of a CE method, resulting in a rapid and efficient optimization of the pH and concentration of the buffer, cyclodextrin concentration and applied voltage.

Topics: beta-Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Propranolol; Regression Analysis; Stereoisomerism

Enantioselective phosphorescence lifetime detection was combined with chiral cyclodextrin-based electrokinetic chromatography for the analysis of camphorquinone (CQ). A time-gated detection system based on a pulsed light-emitting diode for excitation at 465 nm was developed for the online lifetime determination. The background electrolyte for the chiral separation consisted of 20 mM alpha-cyclodextrin (alpha-CD), 10 mM carboxymethyl-beta-CD, and 25 mM borate buffer at pH 9.0. The separation of (+)-CQ and (-)-CQ is caused by a difference in association constants of these enantiomers with alpha-CD. Under the separation conditions, different phosphorescence lifetimes were obtained for (+)-CQ and (-)-CQ (tau = 384 +/- 8 and 143 +/- 5 micros, respectively), which could be used to distinguish the enantiomers. This selectivity in detection is based on a difference in protection of the enantiomers against phosphorescence quenching after their complexation with alpha-CD. Concentration detection limits were 2 x 10(-7) and 1 x 10(-6) M for (+)-CQ and (-)-CQ, respectively. After correction for the lifetime shortening by triplet-triplet annihilation at higher CQ concentrations, a linear dynamic range was obtained from the detection limit up to 2 mM. The system was used to determine the enantiomeric impurity levels of commercial samples of (+)-CQ and (-)-CQ; 0.2% and 0.1%, respectively.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Electrophoresis, Capillary; Limit of Detection; Luminescent Measurements; Molecular Structure; Stereoisomerism; Terpenes

This study outlines a simple method for pH-mediated stacking of natural and synthetic steroids facilitated with carboxymethyl-beta-CD. Sample stacking (10 kV, 60 s) is accomplished with 23 mM carboxymethyl-beta-CD in 50 mM 3-[cyclohexylamino]-1-propanesulfonic acid buffered at pH 10. Following stacking, steroidal compounds are separated in less than 5 min with a running buffer of 13 mM hydroxypropyl-beta-CD, 30 mM SDS in 200 mM phosphate buffered at pH 2.5. Using a 60 s electrokinetic injection, the limits of detection of estradiol, ethynyl estradiol, estrone, hydroxyprogesterone, progesterone, and 11-ketotestosterone range from 2 to 14 nM. For all steroids, the within-day and day-to-day reproducibility in migration time is < or =1 and < or =2% RSD, respectively. The within-day and day-to-day reproducibility in peak area is < or =9 and < or =22% RSD, respectively. The method is applied to fish plasma and holds potential to profile multiple steroids in a single biological sample.

Topics: Animals; beta-Cyclodextrins; Electrophoresis, Capillary; Fishes; Reproducibility of Results; Steroids

A chiral mobile phase HPLC method is described for chiral separation and determination of chlorpheniramine (CP) enantiomers in various commercial preparations. Chromatographic separation was achieved on a conventional ODS column with a mixture of aqueous sodium phosphate (5 mM) containing 0.5 mM carboxymethyl-beta-cyclodextrin, methanol and triethylamine (73:25:2, v/v/v, pH 4.3) as the mobile phase. The flow rate of isocratic elution was 0.24 mL/min and peaks were detected at 224 nm. The method was applied to nine commercial CP preparations in six dosage forms and CP enantiomers were well separated without any disturbance of other ingredients or impurities present. The results showed that only one preparation was d-CP and the others were dl-CP preparations. The contents of all the preparations were found to be in the range of 97%-104% of labeled contents. This method was economical and convenient, affording sufficient accuracy, precision and reproducibility, as well as sensitivity and selectivity.

Topics: beta-Cyclodextrins; Calibration; Chlorpheniramine; Chromatography, High Pressure Liquid; Dosage Forms; Histamine H1 Antagonists; Hydrogen-Ion Concentration; Isomerism; Reproducibility of Results

Carboxymethyl-beta-cyclodextrin (CMCD) has been proposed for remediation of metal-contaminated sediments. This research presents stability constants for CMCD-lead complexes, and demonstrates a rigorous methodology for estimating stability constants for metal-complexing agents. The conditional stability constant for the lead-CMCD aqueous complex was determined to be 10(5.18) with the 95% confidence interval ranging from 10(5.14) to 10(5.22). The best fit for experimental data was made by assuming a reaction between divalent CMCD(2-) and Pb(2+) and using the WATEQ activity coefficient formulation. The optimized value was derived from experimental data with the geochemical model PHREEQC coupled to UCODE_2005, a parameter optimization program. Like FITEQL, UCODE has a built-in option to optimize parameter values by minimizing the weighted sum of squared residuals (WSSR). However, our approach not only allows rapid, automatic optimization of the stability constant, but also allows determination of uncertainties in estimated parameter values and statistical analysis to assess the appropriateness of the conceptual model. The automation of the process allows testing of multiple conceptual models and the final values produced are internally consistent with the PHREEQC database. In this case five different conceptual models to describe the metal complexation and protonation reactions of CMCD were considered.

Topics: Automation; beta-Cyclodextrins; Lead; Metals; Models, Chemical; Models, Molecular; Potassium; Potentiometry; Sodium; Sodium Hydroxide; Solubility; Thermodynamics; Water; Water Pollutants, Chemical; Water Purification

In the present investigation a simple and effective strategy was employed for the development of pH-sensitive self-assembling microparticles based on poly(methacrylic acid) (PMAA)-bis(2-aminopropyl)poly(ethylene glycol) (APEG), and their efficiency in oral protein delivery was evaluated. An inter-ionic gelation process was employed for the preparation of microparticles and particles were obtained spontaneously during the process without using any surfactants or stabilizers. Particle size analysis was carried out to measure average particle size and surface morphology was evaluated using scanning electron microscopy (SEM). Bovine serum albumin (BSA) was incorporated onto these microparticles to evaluate the loading and release properties of the matrix. PMAA-APEG microparticles displayed pH responsive release profile, as less than 10% of encapsulated BSA was released at pH 1.2 in 2 h and more than 80% of loaded protein was released within 3 h at pH 7.4. Carboxymethyl beta-cyclodextrin (CM beta CD)-insulin non-covalent inclusion complex was prepared to enhance the stability of insulin formulations and complex formation was analyzed by fluorescence spectroscopic studies. CM beta CD-complexed insulin was encapsulated into PMAA-APEG microparticles by a diffusion filling method and biological activity of entrapped insulin was evaluated using an ELISA. Finally mucoadhesive studies of PMAA-APEG microparticles were carried out on freshly excised rat intestinal mucosa at neutral pH to establish the adhesive nature of the material.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Cattle; Drug Delivery Systems; Electrodes; Insulin; Microscopy, Electron, Scanning; Particle Size; Polyethylene Glycols; Polymethacrylic Acids; Rats; Serum Albumin, Bovine; Spectroscopy, Fourier Transform Infrared

A high performance liquid chromatographic method to separate the respective enantiomers of paroxetine and its intermediate was developed using chiral mobile phase additive. Separation was performed on a Diamond C18 column (4.6 mm x 250 mm, 5 microm). The mobile phase was 0.1% phosphate acid-methanol (65 : 35, v/v) containing 0.38 g/L carboxymethyl-beta-cyclodextrin and the pH was adjusted to 7.2 by triethylamine. The detection wavelength was set at 210 nm and the temperature was 25 degrees C. With this method, paroxetine's trans/cis isomers and their enantiomers as well as intermediate HFP's trans/cis isomers and their enantiomers were separated simultaneously. The method is simple, rapid with high resolutions.

Topics: beta-Cyclodextrins; Chromatography, High Pressure Liquid; Molecular Structure; Paroxetine; Stereoisomerism; Temperature

This paper investigated the effects of beta-cyclodextrins (beta-CD) and its two derivatives, hydroxypropyl-beta-cyclodextrin (HPCD) and carboxymethyl-beta-cyclodextrin (CMCD), on the solubility and biodegradation of 2-nitrophenyl by an Acinetbacter sp. Results showed that beta-CD, HPCD and CMCD could not be utilized by Acinetbacter sp. as sole carbon source and none of the CDs had toxic effects on the growth of the bacteria in the experiments; all the CDs could enhance the apparent solubility and accelerate the biodegradation of 2-nitrobipheny. It showed that biodegradation-accelerating effects of CDs on 2-nitrobiphenyl were correlated with their solubility-enhancing effects. Among three CDs investigated, CMCD had the most obvious effects both on the apparent solubility and the biodegradation, followed by beta-CD and HPCD.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acinetobacter; beta-Cyclodextrins; Biodegradation, Environmental; Biphenyl Compounds; Nitrogen Compounds; Solubility; Spectrophotometry, Ultraviolet

Reported here is an analytical method enabling the stereochemical resolution of a new antianginal compound possessing two stereogenic centers, leading to four stereoisomers. Only one of these isomers is currently under development as a novel antianginal agent and consequently, the other three isomers are considered as unwanted chiral impurities. Therefore, an enantioselective method is required in order to check its enantiomeric purity. This paper presents a method exploiting the high efficiency of capillary electrophoresis and the complexing properties of cyclodextrins to achieve the separation of the four stereoisomers of this weakly basic compound (pKa = 7.4). For this purpose, the combination of a neutral cyclodextrin, hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), and an anionic cyclodextrin, carboxymethyl-beta-cyclodextrin (CM-beta-CD), was added to the separation buffer running in an uncoated silica capillary. After selection of the suitable cyclodextrin system, satisfactorily separation conditions were as follows: 30 mM phosphate buffer (pH 6.4) containing 10 mM of HP-gamma-CD and 10 mM of CM-beta-CD, running voltage +30 kV. The resulting run time and resolutions were respectively about 17 min and between 1.95 and 2.84. Linearity curves (0.993 < r2 < 0.998) are also shown.

Topics: Angina Pectoris; beta-Cyclodextrins; Cardiovascular Agents; Electrophoresis, Capillary; gamma-Cyclodextrins; Humans; Molecular Structure; Reproducibility of Results; Stereoisomerism

A chiral capillary electrophoresis system allowing the determination of the enantiomeric purity of an investigational new drug was developed using a generic method development approach for basic analytes. The method was optimized in terms of type and concentration of both cyclodextrin (CD) and electrolyte, buffer pH, temperature, voltage, and rinsing procedure. Optimal chiral separation of the analyte was obtained using an electrolyte with 2.5% carboxymethyl-beta-CD in 25 mM NaH2PO4 (pH 4.0). Interchanging the inlet and outlet vials after each run improved the method's precision. To assure the method's suitability for the control of enantiomeric impurities in pharmaceutical quality control, its specificity, linearity, precision, accuracy, and robustness were validated according to the requirements of the International Conference on Harmonization. The usefulness of our generic method development approach for the validation of robustness was demonstrated.

Topics: beta-Cyclodextrins; Buffers; Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Pharmaceutical Preparations; Polyvinyl Alcohol; Reproducibility of Results; Sensitivity and Specificity; Stereoisomerism

The separation and migration behavior of seven positional and structural neutral alkylnaphthalene derivatives in cyclodextrin-mediated capillary electrophoresis were systematically investigated. The effective separation conditions were to use 10 mM phosphate buffer with negatively charged carboxymethyl-beta-cyclodextrin (CM-beta-CD) at pH 6.0. The guest-host interactions with 1:1 or both 1:1 and 1:2 binding stoichiometries for various derivatives were evaluated by comparing their apparent binding constants. The results reveal that the substituent group(s) attached to the naphthalene ring significantly affected the inclusion stoichiometric behaviors. Alkylnaphthalene derivatives with the substituent(s) at the 1-position(s), such as 1-ethylnaphthalene, 1,4-dimethylnaphthalene, may undergo complexation with one and two CM-beta-CD molecules. The binding constants of these derivatives were consistent with the data obtained by a spectrophotometric method. The thermodynamic parameters were also calculated in order to improve our understanding of the interaction between the neutral alkylnaphthalene derivatives and CM-beta-CD at various temperatures. The positive entropy (deltaS degrees) values of the alkylnaphthalenes with the substituent(s) at the 2-position(s) indicate that the inclusion of the guest molecule into the cavity of CM-beta-CD is favored at all temperatures.

Topics: beta-Cyclodextrins; Electrophoresis, Capillary; Naphthalenes; Thermodynamics

A highly new charged cyclodextrin (CD) derivatives, (6-O-carboxymethyl-2,3-di-O-methyl)cyclomaltoheptaoses (CDM-beta-CDs), was synthesized and characterized as anionic reagents for capillary electrophoresis (CE) in an electrokinetic chromatography mode of separation. Substitution with dimethyl groups at the secondary hydroxyl sites of the CD is aimed at influencing the magnitude and selectivity of analyte-CD interactions, while substitution by carboxymethyl groups at the primary hydroxyl sites provides for high charge and electrophoretic mobility. Full regioselective methylation at the secondary hydroxyl sites was achieved in this work, while substitution at the primary hydroxyl sites generated a mixture of multiply charged products. The separation performance of CDM-beta-CD was evaluated using a variety of analyte mixtures. The results obtained from commercially available negatively charged cyclodextrins, heptakis(2,3-di-O-methyl-6-O-sulfo)cyclomaltoheptaose (HDMS-beta-CD) and O-(carboxymethyl)cyclomaltoheptaose (CM-beta-CD) with an average degree of substitution one (DS 1), were compared to CDM-beta-CD using a sample composed of eight positional isomers of dihydroxynaphthalene. Four hydroxylated polychlorobiphenyl derivatives, a group of chiral and isomeric catchecins, and chiral binaphthyl compounds were also separated with CDM-beta-CD. The effect of adding neutral beta-cyclodextrin (beta-CD) into the running buffer containing charged cyclodextrins was investigated and provided evidence of significant inter-CD interactions. Under certain running buffer conditions, the charged cyclodextrins also appear to adsorb to the capillary walls to various degrees.

Topics: Anions; beta-Cyclodextrins; Chromatography; Cyclodextrins; Electrophoresis, Capillary; Isomerism; Models, Molecular; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Quenched phosphorescence detection of camphorquinone in cyclodextrin-based electrokinetic chromatography provides very favorable detection limits, i.e., 7 x 10(-)(7) M, 3 orders of magnitude lower than conventional UV absorption detection at 200 nm. The detection is based on the dynamic quenching by the analyte of the strong phosphorescence emission of brominated naphthalenesulfonate, under deoxygenated buffer solution conditions. This approach has been used to detect (1S)-(+)- and (1R)-(-)-camphorquinone after enantiomeric separation by CE. Although the use of the negatively charged carboxymethyl beta-cyclodextrin (CM-beta-CD) alone was not successful, the addition of a second, neutral cyclodextrin, alpha-CD, provided an adequate enantiomeric separation of camphorquinone. Using 25 mM borate buffer (pH 8.5) with 10 mM CM-beta-CD and 20 mM alpha-CD (applied voltage 20 kV, ambient temperature), the enantiomeric separation was performed in approximately 14 min. The chiral method was applied to monitor the stereoselectivity of the biotransformation of a racemic mixture of camphorquinone by yeast. It was found that the enantiomeric ratio calculated from the peak areas in the electropherogram (RSD = 5%) after 24 h of incubation decreased from 0.92 for the control solution (culture medium without yeast) to 0.24 for the culture medium; a similar ratio of 0.25 was observed for cell extract solutions. Therefore, racemic camphorquinone is enantioselectively degraded by yeast, the biodegradation of (1S)-(+)-camphorquinone being faster than that of the (1R)-(-)-enantiomer.

Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Bromine; Cyclodextrins; Electrophoresis, Capillary; Luminescent Measurements; Molecular Structure; Naphthalenesulfonates; Spectrophotometry, Ultraviolet; Stereoisomerism; Terpenes; Yeasts

Electrokinetic chromatography was employed to separate the enantiomers of two novel functionalized ruthenium(II) complexes with different polypyridyl coordination spheres. The use of anionic carboxymethyl-beta-cyclodextrin as chiral mobile phase additive resulted in maximum efficiency and resolution for the enantiomer separation of both transition metal complexes. The syntheses of the [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(2,2'-bipyridine)rethenium(II)-bis(tetrafluoroborate) and [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(4,4'-dimethyl-2,2'-bypyridine)ruthenium(II)-bis(tetrafluoroborate) complexes and their complete characterization by means of two-dimensional (1)H and (13)C[(1)H] NMR techniques ((1)H-(1)H COSY and (1)H-(13)C HMQC) as well as elemental analyses and MALDI-TOFMS are described in detail. The functionalized complexes can be used as building blocks for further reactions with polymers, biopolymers, surfaces and nanoparticles.

Topics: beta-Cyclodextrins; Chemistry; Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Models, Chemical; Models, Molecular; Ruthenium; Ruthenium Compounds; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stereoisomerism; Time Factors

According to the model of Wren and Rowe, the separation between two enantiomers in capillary electrophoresis (CE) decreases if an organic modifier is added to the run buffer containing a neutral cyclodextrin (CD) in a concentration below its optimal value in a solvent-free system. In previous work, however, it was observed that the addition of methanol to the background electrolyte (BGE) containing not charged carboxymethyl-beta-CD in a concentration below its optimal value, increased the enantioresolution of dimetindene maleate. The enantioresolution decreased when other organic modifiers (ethanol, isopropanol or acetonitrile) were added and/or when other neutral (beta-CD, hydroxypropyl-beta-CD) or chargeable (carboxyethyl-beta- and succinyl-beta-CD) CDs were used. In this CE study further attempts are made to elucidate the observed phenomena through investigating other basic drugs. The effect of organic modifier and CD concentration on the enantioseparation was studied by means of central composite designs. It is shown that obtaining this increase in enantioresolution depends upon the type of CD, the type of organic modifier, and the structure of the analytes. It was also observed that small differences in the structure of the analytes or the CD could have an influence on the enantioresolution. The addition of methanol also resulted in different effects on the resolution of closely related analytes.

Topics: beta-Cyclodextrins; Dimethindene; Electrophoresis, Capillary; Histamine H1 Antagonists; Methanol; Molecular Structure; Stereoisomerism

A capillary electrophoretic method for the chiral separation of enantiomers of synthesized amlodipine and its intermediate was developed. Several cyclodextrins (CDs) were applied as the chiral selectors and it was found that the ionic modified carboxymethyl-beta-cyclodextrin (CM-beta-CD) could give satisfactory enantioselectivity. In addition, the effects of the pH value of the buffer system, the concentration of the CD and the voltage on the chiral separation were investigated. The optimized buffer for amlodipine and its intermediate enantiomers was a buffer containing 30 mmol/L phosphate and 50 mmol/L CM-beta-CD (pH 6.12). Under these conditions, the resolutions of enantiomers of amlodipine and its intermediate were 1.73 and 1.55, respectively.

Topics: Amlodipine; beta-Cyclodextrins; Buffers; Calcium Channel Blockers; Cyclodextrins; Electrophoresis, Capillary; Stereoisomerism

The aim of this work was to optimize conditions for capillary electrophoresis separation of different neurotransmitters (serotonin, phenylalanine, dopamine, adrenaline, ephedrine, propranolol and DOPA) in a single run, including separation of existing enantiomers. As chiral selectors added to the borate background, electrolyte unsubstituted alpha-, beta- and -gamma-cyclodextrins (CDs), methyl-, dimethyl-, and trimethyl-substituted beta-CDs, and hydroxypropyl-substituted alpha-, beta- and gamma-CDs were examined. Also carboxymethyl-beta-CD and succinyl-beta-CD were used for this purpose. In addition to the kind and concentration of chiral selector, some other experimental factors also have been optimized, such as concentration of borate buffer, content of methanol, pH of electrolyte, method of sample introduction into the capillary and washing procedure between consecutive runs. The best results were obtained using 20 mM carboxymethyl-beta-CD in borate buffer of pH 7.5 as running electrolyte and hydrostatic injection. The obtained sensitivity of response (peak height) varied from 0.4 for adrenalines to 2.3 mAU mM(-1) for propranolols. The concentration detection limits (S/N=3) were in the range from 0.04 mM for propranolols to 0.2 mM for adrenalines. The resolution obtained in optimized conditions in a single run was from 0.75 for adrenalins and 1.0 for propranolols up to 2.0 for ephedrines. The developed method was employed for determination of these analytes in brain tissue extracts.

Topics: beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; Neurotransmitter Agents; Sensitivity and Specificity; Stereoisomerism

Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, dynamic capillary electrokinetic chromatography (DEKC) was employed to determine the enantiomerization barrier of thalidomide. In the presence of the chiral mobile phase additive carboxymethyl-beta-cyclodextrin, the interconverting enantiomers of thalidomide produced characteristic elution profiles exhibiting plateaus and/or peak broadening between 25 and 55 degrees C at pH 8. To obtain the enantiomerization barrier of thalidomide from experimental data, the fast and efficient simulation program ChromWin was used to simulate the experimental interconversion profiles and to obtain the apparent rate constants k1app(T). Additionally, these values were compared with the novel approximation function for the direct calculation of enantiomerization barriers from chromatographic parameters of elution profiles. From the rate constants k1app(T) of temperature-dependent measurements the kinetic activation parameters deltaG(T)#,deltaH#, and deltaS# of the enantiomerization of thalidomide were obtained. At 25 degrees C, the enantiomerization barrier deltaG# was determined to be 102 +/- 1 kJ/mol at pH 8 in the dynamic electrokinetic chromatographic experiment.

Topics: beta-Cyclodextrins; Chromatography; Computer Simulation; Cyclodextrins; Hydrogen-Ion Concentration; Sensitivity and Specificity; Stereoisomerism; Temperature; Thalidomide; Thermodynamics

We report on the chiral separation of pharmacologically active dihydropyrimidinones by capillary electrophoresis (CE) using carboxymethyl-beta-cyclodextrin as chiral selector. The influence of selector concentration, pH, and the addition of varying amounts of methanol is investigated. Out of 21 compounds investigated, 19 were resolved, 13 with baseline separation.

Topics: beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Indicators and Reagents; Pyrimidinones; Stereoisomerism

Ritalin, [(+)-threo]methylphenidate hydrochloride, is a chiral drug substance with two chiral centers. The drug substance may contain three pairs of enantiomers, [(+)-threo], [(-)-threo], [(+)-erythro] and [(-)-erythro] isomers, and its degradation products, threoritalinic acid racemate. Determination of the optical purity of ritalin drug substance and the amount of its by-product isomers is a critical step in the single-isomer drug development. In order to efficiently recognize the three pairs of enantiomers by one method, capillary electrophoresis (CE) was employed for the separation. The three pairs of enantiomers in CE showed different enantioselectivities with eight different types of CDs. Only 2,6-di-o-methyl-beta-cyclodextrin (DM-beta-CD) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) showed enantioselectivity to all these pairs of enantiomers. With respect to separation resolution and efficiency, DM-beta-CD was chosen as the chiral selector. For optimization of the separation conditions, the concentration of DM-beta-CD, pH of the buffer solution, and temperature of the capillary were further studied.

Topics: beta-Cyclodextrins; Buffers; Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Indicators and Reagents; Methylphenidate; Stereoisomerism; Temperature

Five cyclodextrin derivatives, namely phosphate ester beta-CD, carboxymethyl-beta-CD(CM-beta-CD), bis-[6-oxygen-(beta-carboxymethyl-succinic acid-4-ester)] beta-CD(F-CM-beta-CD), beta-CD polymer(P-beta-CD), carboxymethyl-poly-beta-CD (CD-P-beta-CD), were used as chiral selector for separation of three basic drugs, lobeline, thiopendonesodium, flunarizine by capillary zone electrophoresis (CZE). All the five cyclodextrins have chiral separation ability to lobeline. P-beta-CD and CM-P-beta-CD have chiral recognition to thiopentonesodium and flunarizine. The results indicate that via optimizing separation conditions by varying pH and the concentration of chiral selectors the three racemic drugs could be baseline separated with 2% P-beta-CD or 0.5% CM-P-beta-CD in the buffer of 30 mmol/L Tris-H3PO4. And the best resolution ranging from 4 to 35 with CM-P-beta-CD as chiral additive was obtained within 10 min. The results were much better than those reported in other references.

Topics: beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; Flunarizine; Lobeline; Stereoisomerism; Thiopental