Topical corneal targeted sustained release amphotericin B liposomal formulation for the treatment of fungal keratitis and its PK-PD evaluation

Abstract

The present study reports topical ocular prolong residence amphotericin B (AB) liposomal formulation. The AB was entrapped within phospholipon-90H-stearylamine-complex (AB-liposome) to form a stable liposome with a size range of 142 ± 0.11 nm. The AB-liposomes powder was prepared by an optimized freeze-drying process with cryoprotectant for reconstitution before use. Liposomes showed biphasic release, initial fast release followed by sustained release. AB-loaded liposomes significantly increase in t1/2 (half-life), MRT (mean residence time) and AUC (area under the curve) in comparison to the current clinically available formulation. PK-PD indices and pharmacokinetic simulation show six ocular instillations/24 h as compared to 24 instillations/24 h by marketed formulations for equivalent efficacy. Thus, phospholipon-90H-stearylamine could be a beneficial strategy for prolong ocular drug delivery and reduce dosing frequency.