Effect Of Various Cyclodextrins Research Articles

Unsaturation of the phospholipid side-chain influences its interaction with cyclodextrins: A spectroscopic exploration using a phenazinium dye

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

Interaction of a phenazinium-based photosensitizer with surface active ionic liquid micelles: Investigating the effect of cyclodextrins on SAIL micelles

The present study depicts a spectroscopic investigation on the binding interaction of a phenazinium-based photosensitizer, phenosafranin (PSF) with a micelle forming surface active ionic liquid (SAIL), 1-butyl-3-methylimidazolium octyl sulfate (Bmim Os). The steady-state as well as time-resolved spectroscopic results reveals the binding of PSF with the micelles of the ionic liquid. The modulations of the spectral properties of PSF on interacting with Bmim Os micelles have been further employed to monitor the effect of various cyclodextrins, αCD, βCD and γCD (with varying dimensions of the hydrophobic cavity), on the Bmim Os micellar aggregates. The effective disruption of the Bmim Os micelles in presence of CDs is confirmed from the reduced size of Bmim Os micelles with added CD as observed from the DLS results.

Improvement of intestinal absorption of curcumin by cyclodextrins and the mechanisms underlying absorption enhancement

Curcumin is known to possess a wide range of pharmacological activities for the treatment of chronic or inflammatory diseases, Alzheimer’s disease, and various cancers. However, the therapeutic efficacy of curcumin is restricted by its poor bioavailability after oral administration. In this study, the effects of various cyclodextrins on the intestinal absorption of curcumin were evaluated in rat intestine by an in situ closed-loop method. Among the tested cyclodextrins, 50 mM α-cyclodextrin significantly enhanced the absorption of curcumin without inducing any intestinal toxicity. The analysis of cellular transport across Caco-2 cell monolayers showed that 50 mM α-cyclodextrin reduced the transepithelial electrical resistance value of cell monolayers and improved the permeability of 5(6)-carboxyfluorescein, a poorly absorbable drug, which is mainly transported via a paracellular pathway. Furthermore, the western blotting analysis showed that α-cyclodextrin decreased the expression of claudin-4, a tight junction-associated protein, in brush border membrane vesicles. Additionally, α-cyclodextrin increased the membrane fluidity of lipid bilayers in brush border membrane vesicles and may also have promoted the permeation of drug molecules via a transcellular pathway. These results suggested that α-cyclodextrin might enhance the intestinal absorption of curcumin via both paracellular and transcellular pathways.

β-Cyclodextrin을 이용한 해수에서의 Prodigiosin의 안정성과 용해도 향상

This research was to examine the effects of various cyclodextrins on the solubility and stability of prodigiosin in seawater. Among them, <TEX>${\beta}$</TEX>-cyclodextrin was found to have the best efficiency and formation of the inclusion complex was saturated when prodigiosin and <TEX>${\beta}$</TEX>-cyclodextrin were mixed in a ratio of 1:8 and shaken at <TEX>$25^{\circ}C$</TEX> and pH 8.0 for 6 h. The maximum algicidal activity against Chattonella antiqua using the inclusion complex stored at <TEX>$4^{\circ}C$</TEX> for 5 weeks of culture was obtained, <TEX>$52.28{\pm}3.41%$</TEX>, which was about 5.0 fold higher than that of control. Our results suggest that inclusion complexes of prodigiosin and <TEX>${\beta}$</TEX>-cyclodextrin could serve as effective algicidal agents.

The Aqueous Solubility and Thermal Stability of α-Lipoic Acid Are Enhanced by Cyclodextrin

We investigated the effects of various cyclodextrins (CDs) on the aqueous solubility and thermal stability of α-lipoic acid, a compound with low water solubility. α-CD, β-CD, and γ-CD had little effect on the aqueous solubility of α-lipoic acid. In contrast, 6-O-α-maltosyl-CDs increased it in a concentration-dependent manner, 6-O-α-maltosyl-β-CD enhancing solubility the most. The thermal stability of α-lipoic acid in the solid state was improved by the addition of G2-β-CD(®), a commercial product of 6-O-α-maltosyl-β-CD. The thermal stability of α-lipoic acid was also improved by the addition of β-CD. Analysis by differential scanning calorimetry showed that G2-β-CD(®), a mixture of maltosyl-β-CDs, and β-CD efficiently formed complexes with α-lipoic acid. These results suggest that the sizes and shapes of these β-CD compounds are compatible with complexation with α-lipoic acid. Moreover, both the formation of an aqueous complex with G2-β-CD(®) and an insoluble complex with β-CD increased the thermal stability of α-lipoic acid.

Effects of various cyclodextrins on the stability of freeze‐dried lactate dehydrogenase

The effects of eight cyclodextrins (CDs) on the stability of freeze-dried lactate dehydrogenase (LDH) were investigated. Five low-molecular weight saccharides were used as a reference. In the samples without saccharides, LDH activity was decreased by freeze-drying. The LDH activities of the samples with 2-hydroxypropylated CDs (HP-CDs) such as 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) showed only a small decrease and were more effective protein stabilizers than low-molecular weight saccharides. HP-beta-CD more effectively stabilized LDH than trehalose, at a sugar concentration of less than 1.0 w/w% and furthermore, a close relationship existed between the highly stabilizing effect and the degree of substitution of polar substituents.

Effect of various cyclodextrins on photodegradation of a hydrophobic herbicide in aqueous suspensions of different soil colloidal components

This paper investigated the photochemical behaviour of the herbicide norflurazon (NFL) in the presence of different soil colloidal components and several cyclodextrins (CDs). The interaction of NFL with CDs yielded the formation of inclusion complexes at 1:1 stoichiometric ratio in solution, with an increase of the herbicide solubility. The irradiation of NFL aqueous solutions in the presence of CDs showed that the higher the formation constant of NFL–CD complexes ( K c) and their solubility, the higher their photocatalytic effects, following the CDs in the order: RAMEB > HPBCD > β-CD > α-CD > γ-CD. The presence of the different soil colloidal components in aqueous suspension provoked the reduction of the NFL photodegradation rate, due to a screening effect, especially when goethite and humic acids were present. No disappearance of NFL was detected in parallel studies carried out in the dark, except in the case of humic acids, where a 5% adsorption of the initial amount of NFL was adsorbed in the dark control. The presence of the different CDs in such systems showed an inductive photodegradation effect on the herbicide. This could be largely explained by the inclusion effects of CDs in catalyzing interactions between NFL and certain reactive radicals generated by the different colloidal components. Although this work was carried out at laboratory scale and therefore, has limited applications, it reveals that cyclodextrins increase solubilization of hydrophobic herbicides and could lead to their increased photodegradation. This could be a promising method for pesticide-contaminated water remediation. However, it is important to consider the effect of the soil colloidal components in the different aquatic systems and their concentrations, since they can alter the photodegradative effects of the cyclodextrins.

Involvement of cholesterol in the inhibitory effect of dimethyl-β-cyclodextrin on P-glycoprotein and MRP2 function in Caco-2 cells

We compared the inhibitory effect of various cyclodextrins (CyDs) on P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) function and examined the contribution of cholesterol to the inhibitory effect of 2,6-di- O-methyl-β-cyclodextrin (DM-β-CyD) on the efflux activity of the function in Caco-2 cell monolayers. Of various CyDs, DM-β-CyD significantly impaired the efflux activity of P-gp and MRP2. DM-β-CyD released P-gp and MRP2 from the monolayers in the apical side’s transport buffer and decreased the extent of cholesterol as well as P-gp and MRP2 in caveolae of Caco-2 cell monolayers, but not caveolin and flotillin-1. On the other hand, DM-β-CyD did not change MDR1 and MRP2 mRNA levels. Therefore, these results suggest that the inhibitory effect of DM-β-CyD on P-gp and MRP2 function, at least in part, could be attributed to the release of these transporters from the apical membranes into the medium as secondary effects through cholesterol-depletion in caveolae after treatment of Caco-2 cell monolayers with DM-β-CyD.

Effect of alpha-, beta- and gamma-cyclodextrins on oxygen evolution by the thylakoid membrane. influence of pH and temperature.

The present work investigates the effect of alpha-, beta- and gamma-cyclodextrins (CD), i.e., alpha-CD, beta-CD and gamma-CD, on the oxygen evolution activity, the protein content and the uv-vis spectroscopic characteristics of thylakoid membranes. To study the pH-dependence, the thylakoids were incubated with the cyclodextrins at 273 K for a period of 10 min in the pH range from 5.5 to 9.0. To study the temperature-dependence the membranes were incubated at 273 and 293 K at pH 6.5, that is, the pH which induces a maximal oxygen evolution in the thylakoid preparations. The major observations are: (i) a stimulation of oxygen evolution in thylakoids incubated with alpha- and beta-CD either in acidic or alkaline conditions, (ii) a low inhibitory effect induced by gamma-CD on oxygen evolution, (iii) a significant decrease of the stimulatory effect of alpha- and beta-CD on oxygen evolution as the incubation temperature is raised from 273 to 293 K, (iv) the apparent inability of the cyclodextrins to change the protein contents of the thylakoids, and (v) a significant CD-induced red-shift from 681 to 683 nm observed in the absorption and second derivative spectra of the thylakoid membranes treated with beta-CD. First, it was found that the temperature effect described here is in accord with the general trend of the chemical effect of various cyclodextrins, i.e., the increase of the CD efficiency with decreasing temperature. Secondly, the CD effect is related to the size of the inner cavity diameter of the cyclodextrin molecules. An important conclusion in this work is that the molecular targets of the cyclodextrins are not limited to the thylakoid lipids as was described previously [Rawyler A. and Siegenthaler PA. (1996) Biochim. Biophys. Acta 1278, 89-97], but are located as well in other molecular species exposed at the stromal side of the thylakoid membrane. In particular, the CD-induced red-shift from 681 to 683 nm in the absorption and second derivative spectra of the thylakoid membranes indicates that the cyclodextrins targets might be either the exposed heme macrocycle in cytochrome b559, or the chlorophylls and pheophytins in the pigment-proteins of the photosystems I and II.

Interaction between cyclodextrins and aflatoxins Q 1, M 1 and P 1: Fluorescence and chromatographic studies

The fluorescence properties of the aflatoxins M 1, Q 1, P 1 in solution and the effect of various cyclodextrins (α-, β-, γ-, hydroxypropyl-β- and α-β-heptakis-di- O-methyl-β-) on their fluorescence emission were studied. Among the aflatoxins, a substantial enhancement of the fluorescence emission of aflatoxin Q 1 in the presence of aqueous solutions of α-, β-, hydroxypropyl-β, and α-β-heptakis-di- O-methyl-β-cyclodextrin, was observed. On the contrary, γ-cyclodextrin proved to be inefficient to enhance the fluorescence properties of this compound. No important fluorescence enhancement was found for aflatoxins P 1 or M 1 for any of the cyclodextrin derivatives tested. The complex formation constant ( K f) of these compounds with β-cyclodextrin was chromatographically determined, and from the results obtained, we can conclude that K f cannot be used alone to explain the fluorescence increase. Thermodynamic studies showed that Δ H and Δ S parameters, associated with the partition of aflatoxins in RP-HPLC, increased when β-cyclodextrin was added to the eluent.

Cyclodextrin complexation of the tetracyanoquinodimethane anion radical: the chemical consequences of cavity size and alkyl derivatization

Optical spectroscopy shows that in aqueous solution the tetracyanoquinodimethane anion radical (TCNQ - ) exist in equilibrium with its π-π dimer (Boyd and Phillips). A study of the effect of various cyclodextrins on this equilibrium shows strilingly different results depending on cavity size and on alkyl derivatization. The equilibrium is unaffected by the presence of α-cyclodextrin. In contrast, γ-cyclodextrin complexes and stabilizes the π-π dimer

Effect of various cyclodextrins on solution stability and dissolution rate of doxorubicin hydrochloride

A number of cyclodextrins were examined as to their ability to stabilize doxorubicin in solution and to enhance the rate of its dissolution. 2-Hydroxypropyl-β-cyclodextrin (HPβCD), 2-hydroxypropyl-γ-cyclodextrin (HPγCD) and γ-cyclodextrin (γCD) all acted to decrease degradation of doxorubicin in solution although the γ-cyclodextrin derivatives were decidedly more effective. Lineweaver-Burk analysis indicated that the incorporated anthracycline degraded 6–10-times more slowly than did doxorubicin in systems which did not contain Cyclodextrin. The chemically modified cyclodextrins were also shown to enhance the rate of dissolution of prototype lyophilized formulations. Thus, HPγCD, present in 5-fold excess relative to doxorubicin, acted to decrease dissolution time from 26 min (for a doxorubicin/lactose dosage form) to less than 9 min. Similarly, HPγCD decreased dissolution time for various prototype formulations. Finally, a complex of HPγCD and doxorubicin was found to be less toxic in a dermal extravasation model. These results, along with the accrued toxicity data which suggest HPγCD is innocuous even when given in large doses parenterally, highly support the use of the modified Cyclodextrin as a stabilizing and dissolution-enhancing excipient.

The effect of cyclodextrins on the rate of intramolecular lactamization of gabapentin in aqueous solution

The effect of various cyclodextrins on the intramolecular lactamization of 3,3-pentamethylene-γ-aminobutyric acid, 1, in solution was investigated. Baseline studies in the absence of cyclodextrins were conducted under accelerated conditions to obtain reaction rates that could be followed over a shorter time interval. In aqueous buffered solutions at 80 ° C and μ = 0.5 M, 1 undergoes an intramolecular aminolysis to yield a stable, cyclized lactam product, 3,3-pentamethylene-γ-butyrolactam, 2A over the pH range of 1.4–11.1. The buffer-independent pH-rate profile was described by two reaction pathways: a specific acid- and specific base-catalyzed lactamization of the uncharged species. Acetate and phosphate buffers were found to catalyze the rate of lactam formation, whereas borate had no apparent catalytic effect. Acetate appeared to be acting as a general-acid catalyst, whereas phosphate appeared to be acting as a general-acid and general-base catalyst. Next, the effect of various cyclodextrins on the lactamization rate was investigated over the pH range of 4.1–7.1. In the pH region defined as specific-acid catalyzed lactamization of the uncharged species, α- and γ-cyclodextrin had minimal effect on the rate, whereas ß- and hydroxypropyl-ß-cyclodextrin accelerated the lactamization rate. While in the pH region defined as specific-base catalyzed lactamization of the uncharged species, all four cyclodextrins catalyzed the reaction rate ( ß- > hydroxypropyl- ß- > α- ≈ γ-cyclodextrin). Interestingly, the catalytic efficiency of acetate buffer varied depending on the cyclodextrin involved. The catalytic efficiency was the greatest in the presence of ß-cyclodextrin which was followed by hydroxypropyl-ß-cyclodextrin. In 100 mM phosphate buffer of pH 7 and in the presence of varying concentrations of the cyclodextrins, the rate of lactamization of 1 exhibited Michaelis-Menten-type kinetics. The data were consistent with relatively weak drug-cyclodextrin complex formation and with 1 being more chemically labile as complexed than uncomplexed drug. The enhanced rate observed in the presence of cyclodextrins was attributed to complexation-induced, conformational changes in the reactive moieties of 1.

Effect of cyclodextrin derivatives on indomethacin stability in aqueous solution.

The effect of various cyclodextrins (CD) and cyclodextrin derivatives on indomethacin stability in phosphate buffer, pH 7.4, was investigated. The influence of CD-ring size, type of substituent, degree of substitution, substitution pattern, and influence of CD concentration were monitored. The indomethacin complex in solution was studied by 1H-NMR spectroscopy to develop a molecular inclusion model. The most favorable ring size for the stabilization of indomethacin was the beta-CD. The beta-CD derivatives inhibited the hydrolysis of indomethacin more effectively than the parent CD. Among the studied CD derivatives, those with lipophilic substituents, such as ethyl or methyl, were superior to those with hydrophilic substitutents. The more hydroxyl groups of the glucose moiety are substituted, the better is the stabilizing effect. Further, the p-chlorobenzoic part of the indomethacin molecule is included in the CD channel.

Stabilization of mitomycins on complexation with cyclodextrins in aqueous acidic media

The effect of various cyclodextrins (α-, β-, dimethyl-β- and γ-cyclodextrin) on the acidic hydrolysis of several mitomycin antibiotics was investigated using a stability-indicating ultraviolet spectrophotometry assay. The mitomycins appear to complexate most prominently with γ-cyclodextrin. Although the degradation pattern does not change, complexation results in a decrease in degradation rate. The influences of the γ-cyclodextrin concentration as well as pH, ionic strength, buffer components and temperature on the complex stability were studied. The structure of the mitomycin C-γ-cyclodextrin inclusion complex has been proposed on the basis of nuclear magnetic resonance spectroscopic measurements.