Poly(2-ethyl-2-oxazoline)-coated solid lipid nanoparticles to enhance ocular delivery of timolol maleate: Design, fabrication and in vitro-in vivo evaluations

Glaucoma, a major cause of irreversible blindness, is primarily managed through pharmacological reduction of intraocular pressure (IOP). However, conventional ophthalmic formulations such as eye drops have poor ocular bioavailability, rapid precorneal clearance, and systemic absorption, leading to suboptimal therapeutic outcomes and poor patient compliance. Timolol maleate, a hydrophilic β-adrenergic blocker, effectively lowers IOP but faces challenges in corneal penetration and sustained ocular retention. To overcome these limitations, poly(2-ethyl-2-oxazoline)-coated solid lipid nanoparticles (PSLNPs) were developed as an advanced nanocarrier system for enhanced ocular delivery of timolol maleate. Utilizing a Box–Behnken Design (BBD), critical formulation variables were optimized to achieve minimal particle size and maximal entrapment efficiency. The optimized PSLNPs demonstrated a mean particle size of 107 ± 17 nm, a zeta potential of −49.6 mV, and an entrapment efficiency of 96.2 ± 0.85%. Invitro drug release studies showed a biphasic release pattern with an initial burst release followed by sustained drug release over 12 h, while ex vivo studies demonstrated significantly enhanced transcorneal and trans-scleral permeation compared to the marketed formulation. The HET-CAM assay confirmed the non-irritant and biocompatible nature of the optimized formulation, supporting its ocular safety. In vivo evaluations further confirmed a prolonged and more pronounced IOP-lowering effect. Overall, the developed PSLNPs represent a promising nanostructured platform for timolol maleate delivery, demonstrating improved ocular bioavailability, enhanced therapeutic efficacy, and reduced dosing frequency for glaucoma management.