Enhancing ocular drug delivery: development and in vivo evaluation of mucoadhesive nanostructured lipid carriers for terbinafine.

Abstract

This study investigated incorporating Terbinafine Hydrochloride (TH) into chitosan-coated nanostructured lipid carrier (NLCs) to improve ocular treatment for fungal keratitis. Solubility studies were conducted to determine the most suitable lipids for NLCs formulation. TH-loaded NLCs were prepared via emulsification followed by ultrasonication. The impact of various lipids and surfactants on the formulation was investigated. The optimal formulation (TH-NLC10) was coated with chitosan (0.5% w/v), resulting in the coated TH-NLC10-CS 0.05% formulation. This formulation was evaluated for physicochemical properties, morphology, in-vitro release, mucoadhesion, permeation, and in vivo efficacy in treating ocular fungal keratitis in rabbits. Results revealed variations in lipids and surfactants significantly affected particle size. All prepared TH-NLCs formulations within the nanometer range. Physicochemical characterizations of the coated TH-NLC10-CS 0.05% showed 88.37 ± 2.41 nm size, 20.2 ± 1.4 mV zeta potential, 93.3 ± 1.5% w/w entrapment efficiency, and spherical morphology. TH-NLC10-CS 0.05% exhibited sustained TH release (66.65 ± 4.3% over 8 h) and strong mucoadhesion as indicated by a decrease in zeta potential from +20.2 ± 1.4 mV to +2.9 ± 0.7 mV. TH-NLC10-CS 0.05% demonstrated a 2.4-fold increase in TH permeation compared to plain TH, along with effective in vivo antifungal activity. This study confirms that mucoadhesive NLCs with TH are promising for the treatment of ocular fungal keratitis.