A 3 super(2) full factorial design for development and characterization of a nanosponge-based intravaginal in situ gelling system for vulvovaginal candidiasis

Clotrimazole (CTZ) is a Biopharmaceutics Classification System (BCS) Class II drug having a limited therapeutic potential because of its poor aqueous solubility and relatively short half-life. The rationale behind the present research effort was to enhance the solubility and efficacy of CTZ by having it form a complex with hydroxypropyl beta -cyclodextrin (HP- beta -CD) nanosponges. Nanosponges (NSs) are hyper-cross linked cyclodextrin polymer-based colloidal structures with three-dimensional networks. Herein, NSs were prepared using dimethyl carbonate as a cross linker, suitably gelled, and were assessed for in vitro release, in vitro bioadhesion, in vivo antifungal activity and in vivoirritation using female Wistar albino rats. Nine formulations were prepared based on a 3 super(2) full factorial design using different Pluronic F-127: Pluronic F-68 ratios. The prepared CTZ-HP- beta -CD NS samples were characterized by carrying out SEM, TEM, and FT-IR spectroscopy studies, as well as DSC and XRPD studies. The average particle size of loaded NS (N6) was found to be 455.6 nm. This sample displayed the lowest polydispersity index of the samples tested, and displayed a high zeta potential (-21.32 plus or minus 1.3 mV), indicative of a stable colloidal nanosuspension. The optimized CTZ NS-based in situgel (F-10) demonstrated prolonged drug release (up to 15 h), considerably longer than that of the conventional in situgel, whose drug release only lasted for less than 6 h. The CTZ-NS gel showed higher in vivoantifungal activity and in vitrobioadhesion than did the conventional in situgel. Furthermore, in vivoirritation studies showed the optimized CTZ NS gel formulation to be a non-irritant. All of these results signified the promising applicability of the formulated CTZ NS gel as a novel delivery system for the local treatment of vaginal candidiasis and other similar infections.