Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery

Abstract

Beta-cyclodextrin nanosponges (NS) based hydrogel had been studied as a topical delivery of ketoconazole (KTZ) for effective eradication of cutaneous fungal infection. The purpose of the present study was to develop KTZ loaded NS for topical drug delivery with skin targeting to minimizing the adverse side effects and providing a controlled release. The four types of NS were synthesized by varying the molar ratios of β-cyclodextrin (β-CD) to diphenylcarbonate (DPC) as a cross linker viz. 1:2, 1:4, 1:6, and 1:8. The KTZ loaded NS shows particle size 274.6-367 nm and high loading efficacy was obtained, FTIR, DSC, XRD studies confirmed the complexation of KTZ with NS. Hydrogel were evaluated comparatively with commercial product with respect to physicochemical properties, ex-vivo skin permeation and skin retention on human cadaver skin and antifungal activity. Ex-vivo study of KTZ-NS hydrogel exhibited controlled drug release up to 8 hrs whereas skin retention studies show avoidance of the systemic uptake and better accumulative uptake of the drug compared to marketed formulation. The zone of inhibition of KTZ-NS hydrogel was higher in comparison with commercial formulation against Candida albicans. These results indicate that the KTZ-NS is having controlled drug release, potential of skin targeting with enhanced antifungal activity.