Stability, biological and biopharmaceutical evaluation of the inclusion complexes of the antifungal and antiprotozoal drug candidate 2-(2-nitrovinyl) furan (G-0) with beta cyclodextrin derivatives

The purpose of this work was to evaluate the inclusion complexes (ICs) of 2-(2-nitrovinyl) furan (G-0) with hydroxypropyl and sulfobutylether-β-cyclodextrin intended for drug stabilization. The freeze-dried ICs were subjected to an accelerated stability study, monitored by HPLC-DAD and GC-MS methods. Drug sublimation/volatility has been analyzed through Thermogravimetric Analysis and Headspace Gas Chromatography. Drug dissolution profile in Simulated Vaginal Fluid (SVF) and permeation/retention in bovine vaginal mucosa were also evaluated. The influence of ICs on the “in vitro” antifungal activity against Candida spp. was investigated through Broth Microdilution Method and the cytotoxicity on fibroblasts and keratinocytes, through MTT assay protocol. ICs ensured an optimum drug chemical stability under accelerated conditions and significantly decreased the drug sublimation/volatilization compared with free G-0 and physical mixtures. Both complexes allowed a fast drug release in SVF, but G-0 was not quantified in the receptor compartment, although it was recovery from the mucosa, without significant influence on the complex formation. ICs maintained the antifungal activity against Candida albicans but improved the drug activity against a Candida krusei resistant strain (ICs MIC = 12.5 μg mL−1, G-0 MIC = 25 μg mL−1, Amphotericin B MIC = 20 μg mL−1). Cytotoxicity on fibroblast and keratinocytes followed the ranking order: G-0 > FD G-0/HP-β-CD > FD G-0/SBE-β-CD. [Display omitted]