Fabricating Niosomes for Ocular Delivery of Clotrimazole: In Vitro Assessment, Ex Vivo Permeation Study, Antimicrobial Efficacy Evaluation, and Histopathological Investigation

Abstract

Niosomes are a novel vesicular drug delivery system made from the self-build of non-ionic surfactants in aqueous media. Niosomes vesicles can encapsulate hydrophilic and lipophilic drugs in an aqueous layer or in vesicular lipid membrane. The purpose in this study was to formulate clotrimazole loaded niosomes using Span 60 with cholesterol in three ratios (w/w) namely; (1:1), (2:1), and (3:1), along with three different amounts of total lipids; 150, 225, and 300 mg. All the prepared niosomal formulas had high encapsulation efficiency (EE%), small vesicle size (VS), and high zeta potential (ZP) values. Software of Design Expert® was utilized for optimization of the prepared niosomes applying 32 complete factorial design. The results showed that the optimized formula is F5, which was composed of Span 60: cholesterol with a ratio (2:1) (w/w) and 225 mg total lipid content. F5 had EE% of 95.83 ± 0.17%, VS of 598.30 ± 7.92 nm, polydispersity index of 0.73 ± 0.07, and ZP of -56.75 ± 2.47 mV. It showed spherical shape carriers without aggregation. Further, a stability study at 4 °C and 25 °C after 45 and 90 days indicated the high stability of F5. Moreover, F5 exhibited a slower in vitro release and a greater permeability across the rabbit cornea compared with clotrimazole suspension. Besides, F5 showed a greater inhibition of Candida albicans development in comparison with clotrimazole suspension, detected via 2,3-bis (2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction method. Additionally, the histopathological inspection on mature male albino rabbits’ eyes verified the safety of F5 after ocular administration.