Maleimide-functionalized phospholipid/Pluronic F127 mixed micelles for efficient ophthalmic delivery of voriconazole against Candida albicans

Drugs that are topically applied on the eyes have low bioavailability, which has always been an important problem. In this study, maleimide functionalized, voriconazole (VCZ) loaded mixed micelles (Mal-VCZ-MM) were designed. Pluronic F127 and phospholipid were used as materials, and maleimide was used as an adhesive. The prepared Mal-VCZ-MM was nearly spherical with a particle size of 84.45 +/- 1.39 nm and a zeta potential of -20.3 +/- 0.29 mV. The encapsulation efficiency of Mal-VCZ-MM was 95.33 +/- 0.06%, and it had high stability with a critical micelle concentration value of 1.28 x 10(-4) mg/mL. CCK-8 assay showed that its cytotoxicity was lower than that of free VCZ solution (VCZ-Sol). Both quantitative and qualitative analyses of the HCE-T cellular uptake showed that the cellular internalization of Mal-C6-MM was significantly stronger than that of C6-MM. The endocytosis pathway was macropinocytosis-mediated, cavernous-mediated, and energy-dependent. In vitro results against Candida albicans showed that the diameters of the antifungal inhibition zones of VCZ-Sol, VCZ-MM, and Mal-VCZ-MM were 15.5 +/- 0.50 mm, 24.0 +/- 0.71 mm, and 31.5 +/- 1.12 mm, respectively. The antifungal effect of Mal-VCZ-MM was significantly higher than that of VCZ-Sol and VCZ-MM (P < 0.001). This study shows that Mal-VCZ-MM is a highly effective hydrophobic ophthalmic drug-delivery carrier that can improve the therapeutic effect of the drug.