Stearylamine-Coated Cationic Phyto-Microemulsions Enhance Resveratrol Ocular Delivery for Glaucoma Therapy: Experimental and Preclinical Insights.

Glaucoma, a leading cause of irreversible blindness, is driven by elevated intraocular pressure (IOP) and oxidative retinal damage. Resveratrol (RES), a polyphenolic antioxidant with neuroprotective activity, offers therapeutic potential but suffers from poor aqueous solubility and low ocular bioavailability. This study developed and evaluated a cationic phyto-microemulsion to enhance ocular delivery of RES. RES-loaded phyto-microemulsion (RES-ME) were formulated using isopropyl myristate, Tween 80, and propylene glycol, with stearylamine (SA) imparting positive surface charge. Optimized uncoated phyto-microemulsion (RTPG) and SA-coated phyto-microemulsion (SRTPG) were characterized for physicochemical properties, mucoadhesive strength, in vitro drug release, ex vivo goat corneal permeation, antioxidant activity, ocular irritation, and IOP-lowering efficacy in a dexamethasone-induced rat glaucoma model. SRTPG exhibited a globule size of 186.2 ± 6.24 nm, PDI 0.147 ± 0.04, and zeta potential + 28 ± 4.56 mV. Drug release was sustained (70-75% over 8 h) and best fitted the Higuchi model (R2 > 0.98). SRTPG achieved markedly higher corneal permeation (750.3 µg/cm2) versus RTPG. HET-CAM and histology confirmed minimal irritancy and preserved corneal architecture. In vivo, SRTPG produced a maximal IOP reduction of 23.88% at 4 h and prolonged efficacy (AUC₀-₈h = 114.28), comparable to dorzolamide. The enhanced performance is attributed to cationic surface charge-mediated mucoadhesion and lipidic microemulsion-facilitated transcorneal transport. SRTPG offer safe, sustained, and penetration-enhanced ocular delivery, with dual IOP-lowering and antioxidant effects, representing a promising nanocarrier platform for glaucoma management.