Optimized delivery of Enalapril Maleate via polymeric Invasomal in-situ gel for glaucoma treatment: In vitro, in vivo, and histological studies

Abstract

Glaucoma is a prevalent ocular condition requiring effective drug delivery systems to overcome the challenges of poor ocular bioavailability and rapid clearance. This study aimed to develop an innovative ophthalmic delivery system utilizing invasomes loaded with Enalapril Maleate to enhance therapeutic outcomes. Enalapril Maleate-loaded invasomes were prepared via a thin-film hydration method, with eight formulae containing varying amounts of terpenes, and evaluated for particle size, surface charge, drug loading efficiency, and in vitro release profile. The optimal formula (F6) was selected using Design Expert software and incorporated into in-situ gel preparations with polymers such as HPMC E15 and Carbopol 940. Compatibility studies of the optimized formulae were conducted using Raman spectroscopy. Among the prepared gels, G3 (containing 1.5 % w/v HPMC E15 and 14 % w/v Pluronic F127) exhibited superior physicochemical characteristics. In vitro and in vivo studies demonstrated that G3, derived from F6, significantly enhanced corneal penetration and prolonged drug release for up to 12 h, effectively reducing intraocular pressure. Histological evaluations revealed improved corneal cell structure in rabbits treated with G3 compared to other groups. The study successfully formulated an in-situ gel containing Enalapril Maleate-loaded invasomes, demonstrating enhanced drug retention, sustained release, and effective intraocular pressure reduction, highlighting its potential as a novel approach to glaucoma management.