gamma-cyclodextrin and hydroxypropyl-gamma-cyclodextrin

We explored the encapsulation of dietary plant flavonols fisetin and its chromophore 3-hydroxyflavone, within 2-hydroxypropyl-γ-cyclodextrin (HPγ-CDx) nano-cavity in aqueous solution using multi-spectroscopic approaches and molecular docking. Upon addition of HPγ-CDx, dramatic changes occur in the intrinsic 'two color' fluorescence behavior of the fluorophores. This is manifested by significant increase in the steady state fluorescence intensities, anisotropies, average fluorescence lifetimes and rotational correlation times. Furthermore, in the CDx environment, intrinsically achiral flavonols exhibit prominent induced circular dichroism bands. These findings indicate that the flavonol molecules spontaneously enter the relatively hydrophobic, chiral environment of the HPγ-CDx nano-cavities. Molecular docking computations corroborate the spectroscopic findings, and predict selectivity in orientation of the encapsulated flavonols. HPγ-CDx inclusion increases the aqueous solubility of individual flavonols ∼100-1000 times. The present study demonstrates that the hydroxypropyl substituent in γ-CDx controls the inclusion mode of the flavonols, leading to their enhanced solubilization and altered spectral signatures.

Topics: Circular Dichroism; Flavonoids; Flavonols; Fluorescence; gamma-Cyclodextrins; Molecular Docking Simulation; Plants; Solubility; Water

Study the complexation of dexamethasone in combinations of γ-cyclodextrin (γCD) and 2-hydroxypropyl-γ-cyclodextrin (HPγCD) with emphasis on solid characterization and development of aqueous dexamethasone eye drop suspension for drug delivery through sclera.. Dexamethasone/cyclodextrin (dexamethasone/CD) solid complex systems were prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and by in vitro drug dissolution testing. Sample eye drop suspensions were prepared applying solubilizer/suspender consisting of γCD/HPγCD mixtures, poloxamer 407 (P407) and polyvinylpyrrolidone. The eye drop suspension was characterized by its physicochemical properties.. The solid characterization techniques applied suggested that solid complexes were being formed. The results indicated that dexamethasone formed non-inclusion or micelle-like aggregates with HPγCD and the γCD/HPγCD mixture. The dissolution and dexamethasone release from the solid dexamethasone/γCD/HPγCD complexes was much faster than from the solid dexamethasone/γCD and dexamethasone/HPγCD complexes. The diameter of the solid particles in the dexamethasone eye drop suspension formulations were in all cases less than 10 μm with a mean diameter from 2.5 to 5.8 μm. The particle size decreased with increasing amount of P407. Permeation studies through semipermeable membrane and porcine sclera showed that increasing the amount HPγCD could enhance drug transport through the membrane barriers and this was related to enhanced drug solubility. The permeation rates were, however, decreased compared to formulation containing γCD alone due to larger hydrodynamic diameter of dexamethasone/γCD/HPγCD complex aggregates. All formulations were both chemically stable for at least 8 months at 25°C and 40°C.. Combination of γCD and HPγCD, i.e., formation of dexamethasone/γCD/HPγCD complexes, resulted in synergistic effect. That is the mixture had greater solubilizing effect than the individual CD, resulted in enhanced dissolution and drug delivery through membranes. Furthermore, it is possible to control the drug release rate by adjusting the γCD:HPγCD ratio in the solid dexamethasone/γCD/HPγCD complexes.

Topics: Animals; Calorimetry, Differential Scanning; Dexamethasone; Drug Compounding; Drug Delivery Systems; Drug Stability; gamma-Cyclodextrins; Glucocorticoids; Micelles; Microscopy, Electron, Scanning; Ophthalmic Solutions; Particle Size; Poloxamer; Posterior Eye Segment; Povidone; Solubility; Spectroscopy, Fourier Transform Infrared; Suspensions; Swine

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

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

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

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

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

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

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

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

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

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