Development and Optimization of Terpene-Enriched Vesicles (Terpesomes) for Effective Ocular Delivery of Fenticonazole Nitrate: In vitro Characterization and in vivo Assessment
Rofida Albash, Abdulaziz Mohsen Al-mahallawi, Mariam Hassan, Ahmed Adel Alaa-Eldin
Abstract
Objective: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection. Methods: Thin film hydration method was used to prepare terpesomes according to a 3 2 full factorial design to inspect the effect of several variables on vesicles’ features. The investigated factors were terpenes type (X 1 ) and terpenes amount (X 2 ) while the dependent responses were encapsulation efficiency percent (Y 1 ), particle size (Y 2 ) and polydispersity index (Y 3 ). Design Expert ® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans ) retained in the tear’s fluid at different time intervals after ocular application in albino rabbits. Results: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02± 2.35%, particle size of 287.25± 9.55 nm, polydispersity index of 0.46± 0.01 and zeta potential of 36.15± 1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes. Conclusion: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate. Keywords: fenticonazole nitrate, histopathological study, ocular drug delivery, microbiological study, terpesomes