Intranasal delivery of epigallocatechin gallate-laden platelet extracellular vesicles for mitigating retinal glaucoma

Abstract

Glaucoma is a serious cause of permanent blindness worldwide, mainly caused by inflammation and degeneration of the optic nerve. However, current treatments using systemically administered drugs have limited effectiveness due to various biological barriers that prevent their biodistribution in the eye. To overcome these challenges, we developed a new therapy that utilizes intranasal delivery to retinal lesions. In this therapy, we used platelet extracellular vesicles (pEVs) as carriers for epigallocatechin gallate (EGCG), which is known for its neuroprotective, anti-inflammatory, and immunomodulatory properties. We hypothesized that this therapy could overcome ocular barriers, increase drug bioavailability, and mitigate glaucoma progression. We conducted extensive characterization of the biochemical and biophysical properties of the EGCG-pEVs, and the results were promising. In vivo tests using an animal model of dexamethasone-induced glaucoma showed that intranasal administration of EGCG-pEVs was safe and had superior drug delivery and therapeutic efficacy, including anti-inflammatory, immunomodulatory, and intraocular pressure-reducing effects, compared to an intraperitoneal injection or ophthalmic drug administration routes. This unique mode of drug administration shows great potential for clinical applications in ophthalmology.