Terconazole loaded edge-activated hybrid elastosome for revamped corneal permeation in ocular mycosis: In-vitro characterization, statistical optimization, microbiological assessment, and in-vivo evaluation.

Abstract

Herein, we investigated the preparation and characterization of Terconazole loaded edge-activated hybrid elastosome (TCN-EHE) adopting thin film hydration technique for the treatment of ocular mycosis. Terconazole (TCN) is a broad spectrum antimycotic agent suffering from sparse aqueous solubility impeding its use in ophthalmic preparations. The scrutinized formulation variables namely X₁: Surfactant: Edge activator ratio (SAA: EA), X₂: Pluronic® L121 contribution (% of total SAA) and X₃: EA concentration (%<i>w</i>/<i>v</i>) were optimized adopting D-optimal design. Ten runs were prepared and characterized regarding their entrapment efficiency, particle size, polydispersity index and zeta potential. An optimized formula was generated, with high desirability, exhibited satisfactory entrapment efficiency, nanoscaled particle size aligning with TEM, plausible zeta potential and bi-phasic release pattern which were not altered after short-term storage. The optimized TCN-EHE displayed 1.94-fold enhanced ex-vivo corneal permeation flux. Safety was ratified through measured corneal hydration level, pH and histopathological evaluation. In-vivo corneal uptake visualized by confocal laser microscopy demonstrated 2.7-fold deeper penetration. Moreover, Superior antifungal activity has been demonstrated displaying 37 % bigger zone of inhibition, 8-fold lower minimum inhibitory and minimum fungal concentration alongside significantly higher biofilm inhibition activity at all tested concentrations for the optimized TCN-EHE compared to TCN suspension. Conclusively, we could prospect that TCN-EHE might be a revamped therapeutic alternative for the delivery of poorly soluble antimycotic agents for the combat of ocular mycosis.