Smart Reactive Oxygen Species-Sensitive Nanoplatforms for Enhanced Ocular Drug Deliver in Glaucoma

Abstract

Glaucoma is a major cause of irreversible blindness and is associated with elevated intraocular pressure (IOP), retinal ganglion cell (RGC) degeneration, and oxidative stress–mediated trabecular meshwork damage. Increased reactive oxygen species (ROS) in glaucomatous tissues have promoted the development of ROS-responsive nanoplatforms for targeted ocular drug delivery. This review summarizes recent advances in ROS-sensitive nanocarriers, including thioketal-linked nanoparticles, boronic ester systems, selenium-based polymers, nano micelles, and hydrogel ocular inserts. Preclinical and in vitro studies evaluating drug release, ocular permeation, IOP reduction, and neuroprotection were critically analysed. ROS-responsive systems demonstrated selective drug
release under oxidative conditions, achieving 70–90% release in high-ROS environments compared with <20% under physiological conditions. Peroxide-sensitive nanoparticles loaded with timolol or latanoprost reduced IOP by 32–45% for up to 7 days. Thioketal nano micelles provided 35–50% RGC protection, while ROS-sensitive ocular inserts sustained therapeutic levels for more than 1 week and reduced dosing frequency. Hybrid nano systems also improved corneal penetration and ocular retention. ROS-responsive nanotechnology represents a promising
strategy for glaucoma therapy by enabling targeted delivery, prolonged drug residence, reduced dosing frequency, and enhanced neuroprotection. Further in vivo and clinical studies are required to confirm long-term safety and translational potential.