Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy.

Tobias Sonntag,W. Daniel Stamer,Franziska Froemel,Rudolf Fuchshofer,Andreas Ohlmann,Miriam Breunig

doi:10.3390/pharmaceutics13060901

Tobias Sonntag, W. Daniel Stamer + Show 4 more

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https://doi.org/10.3390/pharmaceutics13060901

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Abstract

In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload.

Highlights

Primary human trabecular meshwork cells and Schlemm’s canal (SC) cells were fully characterized according to standard methods (PMIDs: 9727403, 29526795) and used until passage number 8
AuNPs were compared to gold carrying on their surexperiments, AuNPs were compared to gold on their surface face (HA-AuNPs)
We successfully investigated the relevance of NP size for targeting the trabecular meshwork after intracameral injection ex vivo

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. With an estimated 60.5 million cases, glaucoma is one of the leading causes of irreversible blindness worldwide [1]. Primary open-angle glaucoma (POAG) is the most prevalent form of glaucomatous diseases [2]. Eye drops are applied as first-line treatment to reduce the intraocular pressure (IOP), which is the major risk factor of the disease. Bioavailability of topically applied drugs in the anterior chamber is only about 1 to 5% [3]

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