ONE-POT FABRICATION OF A BETAXOLOL HYDROCHLORIDE-LOADED NANOSTRUCTURED LIPID CARRIER THERMO-RESPONSIVE OCULAR NANOGEL FOR ENHANCED CORNEAL PERMEATION AND RETENTION

Abstract

Topical treatment of glaucoma is limited by rapid precorneal clearance and poor ocular retention of conventional eye drops. The present study aimed to develop a betaxolol hydrochloride (BH)-loaded nanostructured lipid carrier (NLC) thermo-responsive ocular nanogel using a one-pot fabrication approach integrating NLC formation and gel development within the same processing vessel. The optimized OP-BH-NLC-Tgel formulation exhibited a particle size of approximately 178.27 ± 5.56 nm, low polydispersity, high entrapment efficiency (~96%), and a thermo-responsive gelation temperature of approximately 32–33 °C. The formulation showed pseudoplastic flow and controlled drug release, with only 18% BH release at 30 min compared with 46.2% from Betoptic® 0.25%. Ex vivo evaluation demonstrated significantly enhanced corneal drug permeation compared with Betoptic® 0.25% (p < 0.05) and 2.48-fold greater corneal BH retention. Histopathological examination revealed preservation of corneal architecture without apparent tissue damage following formulation exposure. Furthermore, the optimized formulation exhibited satisfactory preliminary physicochemical stability under room-temperature conditions (25–30 °C) for 6 months, with only minor changes in the evaluated parameters. Overall, the one-pot fabrication approach successfully generated a stable thermo responsive BH-NLC nanogel with controlled drug release and enhanced corneal permeation and retention. The developed system represents a promising topical ocular delivery platform for improving the residence and delivery of BH in glaucoma management.