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Cyclodextrin effects on the ex-situ bioremediation of a chronically polychlorobiphenyl-contaminated soil

The possibility of enhancing the intrinsic ex-situ bioremediation of a chronically polychlorinated biphenyl-contaminated soil by using cyclodextrins was studied in this work. The soil, contaminated with a large array of polychlorinated biphenyls and deriving from a dump site where it has been stored for about 10 years, was found to contain indigenous cultivable aerobic bacteria capable of utilising biphenyl and chlorobenzoic acids. The soil was amended with inorganic nutrients and biphenyl, saturated with water, and treated in aerobic batch slurry- and fixed-phase reactors. Hydroxypropyl-beta-cyclodextrin and gamma-cyclodextrin, added to both reactor systems at the concentration of 10 g/L at the 39th and 100th days of treatment, were found to generally enhance the depletion rate and extent of the soil polychlorobiphenyls. Despite some abiotic losses could have affected the depletion data, experimental evidence, such as the production of metabolites tentatively characterized as chlorobenzoic acids and chloride ion accumulation in the reactors, indicated that cyclodextrins significantly enhanced the biological degradation of the soil polychlorobiphenyls. This result has been ascribed to the capability of cyclodextrins of enhancing the availability of polychlorobiphenyls in the hydrophilic soil environment populated by immobilised and suspended indigenous soil microorganisms. Both cyclodextrins were metabolised by the indigenous soil microorganisms at the concentration at which they were used. Therefore, cyclodextrins, both for their capability of enhancing the biodegradation of soil polychlorobiphenyls and for their biodegradability, can have the potential of being successfully used in the bioremediation of chronically polychlorinated biphenyl-contaminated soils. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

Role of Hydrophobic Effect on the Noncovalent Interactions Between Salicylic Acid and a Series of beta-Cyclodextrins.

The molecular complexation of salicylic acid (o-hydroxybenzoic acid) by beta-cyclodextrin (beta-CD) and/or two of its most used derivatives, 2,6-di-O-methyl-beta-cyclodextrin (DIMEB) and hydroxypropyl-beta-cyclodextrin (HPBCD), was studied from pH potentiometric measurements. The role of the hydrophobic effect was evaluated by studying the influence of the presence of different constant amounts of a series of alcohols (methanol, ethanol, propanol, and butanol) on the CD:guest interaction at 25 degrees C. The study was carried out by measuring the pH of the hydroalcoholic solutions of the guest, whose concentration is kept constant, as a function of cyclodextrin concentration. The dissociation constant of salicylic acid and the binding constants of the inclusion complexes formed by the CD and both the nonionized (HSA) and ionized (SA-) forms of the guest were simultaneously determined at all alcohol concentrations by using a model previously derived by us. The carboxylic forms were found to bind the CD with higher affinities than the carboxylate partners, irrespective of the polarity of the medium and the cyclodextrin used. The ratio KCD:HSA/KCD:SA- is a constant value characteristic of the cyclodextrin, which points to the hydrophobic effect as one of the main forces involved in the association. A clear influence of the solvent polarity on the affinity of binding was found, in the sense that, as long as the medium becomes more apolar, the interaction between the drug and the cyclodextrin is weakened. A phenomenological limit association curve is proposed to define the limiting conditions for association in the presence of an alcohol as a cosolvent. Copyright 1999 Academic Press.

Journal Article↗

Combination of 2D-, 3D-connectivity and quantum chemical descriptors in QSPR. Complexation of alpha- and beta-cyclodextrin with benzene derivatives.

Quantitative models are found to describe the complexation of alpha- and beta-cyclodextrin with mono- and 1,4-disubstituted benzene derivatives by using combinations of 2D-, 3D-connectivity and quantum chemical molecular descriptors. The association constants (K(a)) for the inclusion complexation of cyclodextrins and benzene derivatives are calculated by the models found with a high degree of precision. These models also permit the interpretation of the driving forces of such complexation processes. In the case of the complexation of alpha-cyclodextrin with benzene derivatives these driving forces are mainly the electronic repulsion between frontier orbitals of the host and guest molecules. However, the complexation of beta-cyclodextrin with benzene derivatives is controlled by topological and topographic parameters indicating the relevance of the van der Waals and hydrophobic interactions. We also carried out molecular modeling studies showing that for alpha-cyclodextrin complexes the benzene ring is outside the cavity of the cyclodextrin, while in beta-cyclodextrin they penetrate deeply into the apolar and hydrophobic cavity of the host, which explain the differences in the driving forces for both complexation processes.

Journal Article↗

Chiral recognition of helical metal complexes by modified cyclodextrins.

Chirality of metal complexes M(phen)3(n+) (M = Ru(II), Rh(III), Fe(II), Co(II), and Zn(II), and phen = 1,10-phenanthroline) is recognized by heptakis(6-carboxymethylthio-6-deoxy)-beta-cyclodextrin heptaanion (per-CO2(-)-beta-CD) and hexakis(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TMe-alpha-CD) in D2O. The binding constant (K) for the Delta-Ru(phen)3(2+) complex of per-CO2(-)-beta-CD (K = 1250 M(-1)) in 0.067 M phosphate buffer at pD 7.0 is approximately 2 times larger than that for the Lambda-isomer (590 M(-1)). Definite effects of inorganic salts on stability of the complexes indicate a large contribution of Coulomb interactions to complexation. The fact that hydrophilic Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) does not form a complex with per-CO2(-)-beta-CD suggests the importance of inclusion of the guest molecule into the host cavity for forming a stable ion-association complex. The positive entropy change for complexation of Ru(phen)3(2+) with per-CO2(-)-beta-CD shows that dehydration from both the host and the guest occurs upon complexation. Similar results were obtained with trivalent Rh(phen)3(3+) cation. Pfeiffer effects were observed in complexation of racemic Fe(phen)3(2+), Co(phen)3(2+), and Zn(phen)3(2+) with per-CO2(-)-beta-CD with enriched Delta-isomers. Native cyclodextrins such as alpha-, beta-, and gamma-cyclodextrins as well as heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin do not interact with Ru(bpy)3(2+). However, hexakis(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TMe-alpha-CD) interacts with Ru(phen)3(2+) and Ru(bpy)3(2+) and discriminates between the enantiomers of these metal complexes. The K values for the Delta- and Lambda-Ru(phen)3(2+) ions are 54 and 108 M(-1), respectively. Complexation of the Delta- and Lambda-isomers of Ru(phen)3(2+) with TMe-alpha-CD is accompanied by negative entropy changes, suggesting that cationic Ru(phen)3(2+) is shallowly included into the cavity of the neutral host through van der Waals interactions. The Delta-enantiomer, having a right-handed helix configuration, fits the primary OH group side of per-CO2(-)-beta-CD (SCH2CO2(-) side) well, while the Lambda-enantiomer, having a left-handed helix configuration, is preferably bound to the secondary OH group side of TMe-alpha-CD. The asymmetrically twisted shape of a host cavity seems to be the origin of chiral recognition by cyclodextrin.

Journal Article↗

Molecular printboards: monolayers of beta-cyclodextrins on silicon oxide surfaces.

Monolayers of beta-cyclodextrin host molecules have been prepared on SiO2 surfaces. An ordered and stable cyano-terminated monolayer was modified in three consecutive surface reactions. First, the cyanide groups were reduced to their corresponding free amines using Red Al as a reducing agent. Second, 1,4-phenylene diisothiocyanate was used to react with the amine monolayer where it acts as a linking molecule, exposing isothiocyanates that can be derivatized further. Finally, per-6-amino beta-cyclodextrin was reacted with these isothiocyanate functions to yield a monolayer exposing beta-cyclodextrin. All monolayers were characterized by contact angle measurements, ellipsometric thickness measurements, Brewster angle Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry, which indicate the formation of a densely packed cyclodextrin surface. It was demonstrated that the beta-cyclodextrin monolayer could bind suitable guest molecules in a reversible manner. A fluorescent molecule (1), equipped with two adamantyl groups for complexation, was adsorbed onto the host monolayer from solution to form a monolayer of guest molecules. Subsequently, the guest molecules were desorbed from the surface by competition with increasing beta-cyclodextrin concentration in solution. The data were fitted using a model. An intrinsic binding constant of 3.3 +/- 1 x 10(5) M(-1) was obtained, which corresponds well to previously obtained results with a divalent guest molecule on beta-cyclodextrin monolayers on gold. In addition, the number of guest molecules bound to the host surface was determined, and a surface coverage of ca. 30% was found.

Journal Article↗

Cyclodextrin derivative-coated quartz crystal microbalances for alcohol sensing and application as methanol sensors.

Three novel cyclodextrin derivatives, mono(6-benzylimino-6-deoxy)-beta-cyclodextrin (2), mono-(6-cyclohexylamino-6-deoxy)-beta-cyclodextrin (3) and mono(6-benzylamino-6-deoxy)-beta-cyclodextrin (4), together with mono(6-phenylamino-6-deoxy)-beta-cyclodextrin (1), were synthesized and employed as sensing materials coated on quartz crystal microbalances (QCMs). Comparison of the responses to some alcohol and solvent vapours such as methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, acetone, chloroform and benzene indicated that these beta-cyclodextrin derivatives show considerable sensitivity and selectivity towards methanol. It shows a good linear relationship between the frequency shift and the methanol concentration in the range 3-160 mg L(-1) for 2-4 and 3-140 mg L(-1) for 1. The correlation coefficients are 0.9971, 0.9983, 0.9973 and 0.9977, respectively. The limit of detection (LOD) is 0.2 mg L(-1). When small amounts of other vapours co-exist, e.g., ethanol, propan-1-ol and acetone, the responses differ from that of pure methanol vapour, and a deduction method could eliminate this cross-sensitivity. The water cross-sensitivity was very low. These QCMs coated with cyclodextrin derivatives are employed as methanol sensors in the real atmosphere to detect on-line the concentration of methanol vapour.

Air Pollutants, Occupational↗

A comparison of nimesulide beta cyclodextrin and nimesulide in postoperative dental pain.

The aim of this study was to assess the efficacy and tolerability of single doses of nimesulide beta cyclodextrin compared with nimesulide in patients with dental pain following surgical procedures. This was a randomised, double-blind, between-patient, multicentre study involving 148 outpatients suffering from moderate to severe pain, who received single doses of either 400 mg nimesulide beta cyclodextrin or 100 mg nimesulide. The principal criterion for efficacy was pain intensity assessed on a visual analogue scale (VAS) 15 minutes after drug intake. Pain intensity was further evaluated 30, 45, 90, 120, 180, 240 and 360 minutes after dosing. Pain relief was evaluated at the same time points by means of a categorical scale. The time point of first pain relief, the use of rescue medication and the global evaluation of efficacy were also recorded. The reduction in pain intensity was significantly more pronounced in the nimesulide beta cyclodextrin group at 15, 30, 45 and 60 minutes (p < 0.01). Pain relief was significantly greater (p < 0.05) and more rapid with nimesulide beta cyclodextrin. In the patient overall assessment of efficacy, nimesulide beta cyclodextrin and nimesulide were rated excellent or good by 95% and 92% respectively; only one patient in the nimesulide beta cyclodextrin group needed rescue medication. Both study drugs were effective and well tolerated in the treatment of acute dental pain, with nimesulide beta cyclodextrin showing a faster onset of analgesic action.

Adolescent↗

Separation of cefoperazone enantiomers using beta-cyclodextrin as chiral additive by capillary zone electrophoresis.

A capillary electrophoresis method was developed to separate the enantiomers of cefoperazone. Different cyclodextrins, including alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and methyl-beta-cyclodextrin (Me-beta-CD), were tested as chiral additives in the running buffer. The effect of various parameters on enantioseparation such as concentration of NaH(2)PO(4), buffer pH, and CD concentration was also studied. The cefoperazone enantiomers were baseline separated under conditions of 0.04 mmol/L beta-CD, 75 mmol/L NaH(2)PO(4) buffer at pH 4.0. A fused silica capillary (40 cm effective length x 75 microm ID) was used. The applied voltage and capillary temperature were 20 kV and 25 degrees C, respectively. Under these conditions, linear calibration curves were obtained in the 5-500 microg/ml range using UV detection at 280 nm. The limit of detection for both isomers was 0.1 microg/ml. The method was used for the analysis of different pharmaceutical preparations (dose) and biological samples containing cefoperazone.

Anti-Bacterial Agents↗

Cyclodextrins as selectivity enhancers in capillary zone electrophoresis of proteins.

The selectivity in the capillary zone electrophoresis (CZE) of a variety of acidic and basic proteins including alpha-chymotrypsinogen A, cytochrome c, lysozyme, ribonuclease A, ovalbumin, and beta-lactoglobulins A and B, was altered by adding 6-monodeoxy-6-monoamino-beta-cyclodextrin or carboxymethylated beta-cyclodextrin to the electrophoretic medium of aqueous 50 mM sodium phosphate, pH 2.5. On the other hand, no significant improvement was obtained in the separation upon addition of heptakis (2,6-di-O-methyl)-beta-cyclodextrin. Whereas protein adsorption on the wall of raw silica capillaries was significant in the absence of cyclodextrin, by addition of beta-cyclodextrin or its derivatives to the background electrolyte, wall adsorption was reduced with concomitant enhancement of the recovery. The results confirm that in various separation techniques, particularly those which employ microcolumns, certain cyclodextrin additives can be useful selectivity enhancers not only in the separation of small sample molecules but also in that of proteins.

Adsorption↗

Enantiomeric separation of neutral hydrophobic dihydrofuroflavones by cyclodextrin-modified micellar capillary electrophoresis.

The enantiomeric separations of several very hydrophobic dihydrofuroflavones were performed and optimized using cyclodextrin-modified micellar capillary electrophoresis. Overall, the greatest enantiomeric peak-to-peak separations for the greatest number of flavones were obtained with hydroxypropyl-gamma-cyclodextrin. The effects of cyclodextrin and sodium dodecyl sulfate concentration and pH were examined in order to optimize the separation conditions. The ratio of surfactant-to-cyclodextrin concentration affected the chiral discrimination of the system significantly, with increases in the derivatized cyclodextrin concentration generally enhancing resolution. Higher efficiencies were obtained with lower concentrations of surfactant and cyclodextrin, although enantioseparation optimization often required higher concentrations to be used. A highly acidic pH was necessary to effectively suppress the electroosmotic flow when operating in the reversed polarity mode. Experiments utilizing the normal polarity mode and higher pH produced no separations.

Buffers↗

Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

Administration, Oral↗

Chiral separation of the four stereoisomers of a novel antianginal agent using a dual cyclodextrin system in capillary electrophoresis.

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.

Angina Pectoris↗

Expression of ACTH-induced corticosteroid biosynthesis in newborn rat adrenocortical cells cultured in serum-free and carrier protein-free medium containing a cholesterol-alpha-cyclodextrin complex.

Newborn rat adrenocortical cells were successfully cultured in a serum-free carrier protein-free medium (SPFM) by using alpha-cyclodextrin as a cholesterol carrier and have expressed corticosteroid biosynthesis in this medium. A stable inclusion complex of cholesterol-alpha-cyclodextrin with a molar ratio of almost 1 was obtained for a 5 X 10(-5) mol/1 alpha-cyclodextrin concentration. Cell cultures incubated with [4-14C] cholesterol-alpha-cyclodextrin in SPFM produced, under ACTH stimulation, various 14C labeled steroids with a predominance of corticosterone and 18-hydroxy-11-deoxycorticosterone. As measured by gas chromatography and mass spectrometry, the ratio between corticosteroids (21-hydroxylated steroids) and 20 alpha-reduced steroids produced in SPFM with cholesterol-alpha-cyclodextrin was equal to 1.8. This corresponds to a value of 3.6 times higher than that found in the serum-free medium with cholesterol-albumin. Consequently, the chemically defined SPFM with cholesterol-alpha-cyclodextrin used in this study is more suitable for corticosteroidogenesis by adrenal cells in culture than a serum-free medium with cholesterol-albumin.

Adrenal Cortex↗

Oral bioavailability of CHF1194, an inclusion complex of piroxicam and beta-cyclodextrin, in healthy subjects under single dose and steady-state conditions.

CHF1194 is an inclusion complex of beta-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, beta-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-beta-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of beta-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5'-hydroxypiroxicam and beta-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80-125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5'-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with beta-cyclodextrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Methylated beta-cyclodextrins are able to improve the nasal absorption of salmon calcitonin.

The absorption enhancing effect of methylated beta-cyclodextrins on the nasal absorption of salmon calcitonin (sCT) was studied in rats and rabbits. The nasal absorption of sCT following administration without additives was low in both species. The absorption in rats could be largely improved by coadministration of cyclodextrins as apparent from the effect on serum calcium concentrations. Trimethyl-beta-cyclodextrin (TM beta CD), at a concentration of 5% (w/v), was the least potent enhancer. Randomly methylated-beta-cyclodextrin (RM beta CD) and dimethyl-beta-cyclodextrin (DM beta CD), all at a concentration of 5% (w/v), were almost equally effective in decreasing serum calcium levels, and the hypocalcemic responses were similar to those of i.v. and s.c. injected sCT. Absorption enhancement was already achieved with 1% DM beta CD added to the nasal formulations. In rabbits, only the effect of DM beta CD on the nasal sCT absorption was investigated. A total serum calcium decrement in 4 hours of 9.4 +/- 3.9% (mean +/- SD) was observed following nasal administration of 12.6 IU/kg sCT with 5% DM beta CD, comparable to that of i.v.-injected sCT. In conclusion, the methylated cyclodextrins DM beta CD and RM beta CD are suitable absorption enhancers for nasal sCT administration, which is expected to have a clinical impact on the therapy with calcitonin.

Absorption↗

[Comparative endoscopic study of gastroduodenal tolerance of piroxicam-beta-cyclodextrin vs piroxicam].

The gastroduodenal tolerability of piroxicam-beta-cyclodextrine was evaluated in a double-blind, parallel group study in 32 healthy male volunteers. The doses used were 20 mg piroxicam-beta-cyclodextrin vs 20 mg piroxicam daily over a period of 14 days. Gastric tolerability was assessed by using upper endoscopy. Gastroscopy was performed at base-line and after the dosing period of 14 days. The mucosal lesions were scored using modified Lanza criteria. In comparison to piroxicam, piroxicam-beta-cyclodextrine was significantly better tolerated after a 14 day dosing period. Mean gastric-duodenal score: Piroxicam-beta-cyclodextrine 3 +/- 4 (median 1), piroxicam 6 +/- 4 (median 8). The score values for the stomach were for piroxicam-beta-cyclodextrin 2 +/- 3 (median 1) and for piroxicam 4 +/- 3 (median 6). The corresponding values for the duodenal bulb 2 +/- 4 (median 0) and 4 +/- 5 (median 0), respectively. Both drugs averaged were generally well tolerated. In summary, piroxicam-beta-cyclodextrin given as a 20 mg single oral morning-dose over a 14-day period was significantly better tolerated than piroxicam 20 mg with regard to gastroduodenal damage.

Adult↗

Pressure-controlled high-performance liquid chromatographic study on the influence of rim chemistry on partial molar volume differences between free and complexed cyclodextrins.

Pragmatic comparison of pressure dependent retention for differing cyclodextrin rim chemistries is assessed using controlled-pressure HPLC. For pressure differences of <300 bar, systematic shifts in solute capacity factor are observed for both native and methylated beta-cyclodextrin stationary phases. In addition to the importance of this observation for the practice of liquid chromatography, this technique can also be implemented in the fundamental determination of the influence of rim chemistry on the cyclodextrin partial molar volume both with and without solute inclusion. That is, pressure-controlled measurements provide a direct comparison between the partial molar volumes for native cyclodextrin (CD) and methylated cyclodextrin (MCD) in the presence and absence of the complexing solute (comp). Surprisingly, direct comparison of the measured partial molar volumes for the two rim chemistries indicates that the presence of neutral solutes does not contribute significantly to the volumetric component of complexation, V(comp,CD) - V(comp,MCD) approximately V(CD) - V(MCD). In contrast, their ionized counterparts are shown to exhibit marked rim chemistry differences in the partial molar volume of cyclodextrins with and without anion inclusion, V(comp(-),CD) - V(comp(-),MCD) < V(CD) - V(MCD). Not previously demonstrated by direct chromatographic measurement, these results have interesting implications for advancing the fundamental understanding of host-guest solvation properties.

Chemical Phenomena↗

Poly(acrylic acid) microspheres containing beta-cyclodextrin: loading and in vitro release of two dyes.

Microspheres containing poly(acrylic acid) and beta-cyclodextrin or maltose were prepared by a w/o solvent evaporation technique. The dispersed aqueous phase contained poly(acrylic acid) (800 mg) and beta-cyclodextrin or maltose (0, 200 or 800 mg). Food-grade olive oil was the continuous phase. Microsphere particle size was consistently between 15 and 25 microm, and carbohydrate content was in good agreement with that added to the dispersed phase in all cases. Two dyes, phenolphthalein and rhodamine B, having different solubility characteristics and strengths of association with beta-cyclodextrin, were selected for loading and in vitro release studies. Microspheres were loaded by soaking in a saturated propan-2-ol solution of the appropriate dye (6 h). Microsphere dye content ranged between 2.8 and 4.8 mg/g microspheres for phenolphthalein and between 2.2 and 3.7 mg/g for rhodamine B. Release studies were performed in phosphate buffer (pH 7.4; 37 degrees C). No difference in the release profile of either dye was observed between microspheres. The failure of microspheres containing beta-cyclodextrin in particular, to alter the in vitro release kinetics of either dye may be due to a number of factors and include: (i) limited cross-linking giving rise to a the rapid hydration of the polymer matrix; (ii) perturbation of the dye-beta-cyclodextrin complex by oil and/or organic solvent residues; and (iii) conformational changes/steric hindrance of the beta-cyclodextrin cavity (due to its covalent binding with PAA) resulting in a reduction in its ability to form inclusion complexes.

Acrylic Resins↗