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 X 1 : Surfactant: Edge activator ratio (SAA: EA), X 2 : Pluronic® L121 contribution (% of total SAA) and X 3 : EA concentration (% w / v ) 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.

Topics & Concepts