Active trans-corneal drug delivery with ocular adhesive micelles for efficient glaucoma therapy.

Abstract

Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)-block-poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.