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

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 <i>via</i> 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 <i>in vivo</i> 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 <i>in vivo</i> antifungal activity. This study confirms that mucoadhesive NLCs with TH are promising for the treatment of ocular fungal keratitis.