Liposomal voriconazole (VOR) formulation for improved ocular delivery

Area of Science:

• Ophthalmology
• Pharmaceutics
• Drug Delivery Systems

Background:

• Topical eye treatments face challenges due to the eye's natural defense mechanisms, which limit drug absorption and residence time.
• Fungal keratitis requires effective drug delivery to overcome these barriers and improve patient outcomes.
• Conventional topical therapies may not achieve sufficient drug concentrations in the cornea.

Purpose of the Study:

• To develop and characterize liposomal voriconazole (VOR) formulations for topical ocular delivery.
• To evaluate the efficacy of these liposomes in overcoming ocular defense mechanisms and treating fungal keratitis.
• To assess the stability, safety, and permeation characteristics of the liposomal VOR formulation.

Main Methods:

• Liposomes encapsulating voriconazole (VOR) were prepared using soy phosphatidylcholine (PC), DOTAP, and cholesterol.
• Formulations were characterized for entrapment efficiency (EE), drug recovery (DR), size, polydispersity index (PdI), and zeta potential.
• In vitro mucosal interaction, ex vivo corneal permeation, and short-term stability (solution and lyophilized) were evaluated.

Main Results:

• The optimal liposomal VOR formulation exhibited a mean size of 116.6nm, narrow PdI (0.17), and high EE (>80%).
• The formulation demonstrated good stability in solution (30 days) and after lyophilization (90 days).
• It was classified as non-irritant and achieved significant VOR permeation into porcine cornea (47.85μg/cm²), exceeding fungal minimum inhibitory concentrations (MICs).

Conclusions:

• Liposomal VOR formulations are a promising strategy for topical treatment of fungal keratitis.
• These liposomes enhance drug penetration and stability, potentially improving therapeutic efficacy.
• The developed formulation offers a viable alternative to conventional treatments for infectious eye diseases.