Development of acetazolamide loaded bilosomes for improved ocular delivery: Preparation, characterization and in vivo evaluation

Abstract

Acetazolamide (ACZ), a carbonic anhydrase inhibitor, is employed to decrease the intraocular pressure (IOP) in glaucoma patients. ACZ is characterized by low aqueous solubility and reduced corneal permeation. The aim of the present work is to incorporate ACZ into bilosomes to achieve improved ocular delivery. ACZ bilosomes were prepared by the thin film hydration method using Span 60, cholesterol along with various bile salts (sodium cholate, sodium deoxycholate, sodium taurocholate and sodium tauroglycocholate) at two molar ratios (1:1:0.1 and 1:1:0.2). The obtained vesicles exhibited high entrapment efficiencies (69.03–74.24%), nanometric vesicle diameters (350–735 nm) with monodisperse distribution, zeta potential values < -43.4 and spherical morphology under transmission electron microscopy. In vitro drug release profiles revealed a biphasic release pattern governed by a Fickian diffusion mechanism. Biological evaluation of the optimized ACZ bilosomal formulation was conducted using male albino New Zealand rabbits, where an improved and extended lowering effect of IOP in comparison to plain ACZ, marketed dorzolamide eye drops as well as marketed ACZ oral tablets, was shown. Moreover, ocular Draize irritancy assessment confirmed the safety of the optimized bilosomal formulation post ocular instillation. Consequently, the developed bilosomal formulation could be considered as a promising nanocarrier for ocular delivery of ACZ for management of elevated IOP.