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Abstract  Nanosponges are betacyclodextrins crosslinked with carbonate bonds. The polymer formed is nanoparticulate in nature. Itraconazole is a BCS Class II drug that has a dissolution rate limited poor bioavailability. Rationale of the work was to enhance the solubility of Itraconazole so that the bioavailability problems are solved. Solid dispersion technique has been used for drug incorporation. The effect of a ternary component copolyvidonum on solubility of itraconazole has been studied. Phase solubility studies has been carried out with a rationale of comparing the solubilization efficiency of nanosponges, copolyvidonum and combination. The dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and photon correlation spectroscopy (PCS). It was found that the solubility of itraconazole was enhanced more than 50-folds with a ternary solid dispersion system. Using copolyvidonum in conjunction with nanosponges helps to increase the solubilization efficiency of nanosponges as evident from the phase solubility studies. [ABSTRACT FROM AUTHOR]

Abstract  We describe improved syntheses of CD derivatives, like 6I-monotosyl, 6I-monoazido-6I-monodeoxy, 6I-monoamino-6I-monodeoxy-βCD and 2I-O-mono(methylamino)alkyl-βCDs, that were carried out under US or MW, to great advantage in terms of yield, purity and reaction time. In the search for more efficient procedures to prepare monosubstituted CDs, we applied MW and/or US to some fundamental preparations such as those of 6I-amino-6I-deoxy-βCD and a series of 2-monoaminomethyl-βCD derivatives. [ABSTRACT FROM AUTHOR]

Abstract  Three alkylcarbonates of γ-cyclodextrin, i.e. hexyl, octyl and dodecylcarbonate, were synthesized and characterized, with the goal of formulating solid nanoparticles. The series of alkylcarbonates showed amphiphilic properties and were capable of forming micelles and nanoparticles. Blank and drug-loaded alkylcarbonate nanoparticles were prepared with each alkylcarbonate, using the solvent injection technique. Progesterone was chosen as model drug. The sizes of both unloaded and loaded nanoparticles were in the 80–200 nm range, with narrow size distribution and spherical shape, as shown by TEM analysis. The zeta potentials of unloaded nanoparticles were in the −20 to −24.0 mV range, and were slightly decreased in loaded nanoparticles. Drug-loading capacity was good; DSC analysis did not detect the progesterone melting peak, indicating the drug had interacted with the cyclodextrin alkylcarbonates. In vitro release kinetics of progesterone from the three types of nanoparticles were slow. These results indicate that γ-CD alkylcarbonate nanoparticles might be used as prolonged drug delivery system. [ABSTRACT FROM AUTHOR]

Oxidative couplings of 2-naphthol, 6-bromo-2-naphthol and 2-naphthylamine were achieved at room temperature in the presence of H2O2, horseradish peroxidase and a suitable cyclodextrin. 2-Thionaphthol behaved differently, yielding the corresponding disulfide. Yields of binaphthyl derivatives were generally excellent, and a fairly good enantiomeric excess was observed. Under similar reaction conditions methyl 2-(6-methoxy-2-naphthyl) propanoate, when treated with esterase in the presence of cyclodextrin, yielded naproxen (a well-known anti-inflammatory drug) with a good enantiomeric excess. No reaction product was detected in the absence of cyclodextrin. Cyclodextrins do not act as simple transfer agents. [ABSTRACT FROM AUTHOR]

Optically pure binaphthyl structures make up the most important family of auxiliaries, ligands and catalysts used in enantioselective reactions. Syntheses of 2,2'-disubstituted-1,1'-binaphtyl derivatives were carried out one pot in water by oxidative coupling with FeCl3 in the presence of β- and γ-cyclodextrin (CD) derivatives. A new efficient and inexpensive preparation of trihydroxyethyl- and tri-2-hydroxypropyl- β- and γ-CD afforded these powerful solubilizing agents. The resolution of racemic 2,2'-dihydroxy-1,1'-binaphthyl was easily achieved by semipreparative HPLC separating diastereomers obtained from the reaction with (-)menthyl chloroformate. Final basic hydrolysis afforded the enantiomerically pure product. [ABSTRACT FROM AUTHOR]

New alkyl carbonates of γ-cyclodextrin have been obtained. These derivatives show lower haemolytic effect than the parent γ-cyclodextrin. The complexation behaviour was tested with three important drugs, namely: progesterone, diazepam and flurbiprofen. DSC analyses were consistent with the inclusion complex formation. [ABSTRACT FROM AUTHOR]

Objective. Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. Methods. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. Results. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-α in up-regulating OPG production. Conclusions. Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA. [ABSTRACT FROM AUTHOR]