Graphene Oxide Nanosheets Incorporated Jasmine Floral Wax and Castor Oil-Based Thermoreversible Oleogel for Improved Corneal Permeation of Ketoconazole: In-vitro-ex-vivo Characterization and Antifungal Study

Abstract

The targeted delivery of drugs to ocular tissue has garnered significant attention for treating ocular diseases. Traditional ophthalmic formulations have various drawbacks, such as low absorption, limited corneal permeation, and rapid removal of the dosage from the ocular cavity. Recently, the scientific community has shown interest in using oleogels for managing ocular infections, although there is a prerequisite for further enhancement in corneal permeation. Graphene oxide (GO) has gained significant attention in drug delivery due to its excellent biocompatibility, aptitude to enhance permeation, and surface tunability. In this research work, we developed an oleogel based on GO, jasmine floral wax (JFW), and castor oil (CO) to improve corneal permeation for targeted delivery of ketoconazole (KTZ). In brief, the prepared GO-KTZ-JFW/CO oleogel underwent various spectral characterizations, antifungal studies, in vitro release assessments, ex vivo permeation experiments, etc. The obtained results revealed that the GO-KTZ-JFW/CO oleogel exhibited good antifungal activity against Candida albicans, attributed to the combination of GO and KTZ. Furthermore, in vitro studies confirmed that 66.33 ± 1.88% of KTZ was released within 6 h (best-fit model: Korsmeyer peppas; 0.991), following a non-Fickian diffusion mechanism (n = 0.554) in oleogels. Notably, the GO-KTZ-JFW/CO oleogel (batch: JC5) significantly improved the ex vivo permeation of KTZ molecules through the caprine cornea. Therefore, this study highlights the presence of GO in oleogels contributes to the enhancement of trans-corneal permeation of KTZ. In conclusion, the GO-KTZ-JFW/CO oleogel demonstrates improved corneal permeation of KTZ and good antifungal ability, marking a potential avenue for ophthalmic oleogels.