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.

Purpose Decisive events of primary open angle glaucoma (POAG) onset and progression are located in the anterior chamber of the eye. Here, the outflow of aqueous humor through the trabecular meshwork (TM) and Schlemm´s canal (SC) is severely impeded.1 Conventional therapy suffers from poor compliance, low bioavailability of drugs, and does not treat the root cause of the disease. In the past few years, targets molecules and structures were identified that are associated with pathological changes of POAG and that could potentially be exploited for causative treatment.2 To efficiently address these novel targets and bring dug molecules to the TM and SC, the development of innovative and tailor‐made drug delivery systems is a prerequisite. Therefore, the goal of this study to exploit nanoparticles of different size and surface modification regarding their efficacy to accumulate in the TM after intracameral injection. Methods Polymer nanoparticles decorated with either hyaluronan or poly(ethylene imine) (PEI; about 250 nm) or gold nanoparticles of 5 nm were injected into the anterior chamber of enucleated porcine eyes. After 5 hr the anterior chamber was dissected and the iris, cornea, lens, the ciliary body and trabecular meshwork were analyzed either by fluorescence microscopy for polymer nanoparticles or inductively coupled plasma mass spectroscopy (ICP‐MS) for gold content. Results Nanoparticles decorated with hyaluronan demonstrated a favorable mobility in the extracellular matrix and excellent accumulation in the TM.3 Gold nanoparticles of 5 nm were detected in the TM at higher amounts compared to other tissues of the anterior chamber. Conclusion Nanoparticles depending on their size and surface modification are promising carriers for therapy of POAG to deliver drugs with high specificity to the TM and SC.