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

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.

Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment

“…For this reason, the ocular tolerability of the nanoparticle formulation should be taken into consideration before in vivo application. Fibroblasts served as a disease model for glaucomatous cells due to the fact that cells in the trabecular meshwork increasingly acquire the phenotype of contractile myofibroblasts during glaucoma development (Sonntag et al., 2021 ).…”

Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

“…For instance, Apaolaza et al [ 55 ] immobilized low molecular weight HA (5 kDa) on the surface of GNPs and visually observed that HA passivation promoted enhanced particle distribution across the vitreous matrix and ocular tissues after local injection in ex vivo porcine eyes. Sonntag et al [ 56 ] also conjugated thiolated HA to GNPs of various sizes (5, 60, 80, and 120 nm) and quantified their distribution in the anterior chamber of the eye in an ex vivo porcine model. The authors found that the HA coating prevented aggregation of NPs inside the trabecular meshwork and yielded reduced gold content in off-target tissues in the anterior eye, such as the cornea, lens, iris, and ciliary body.…”

Contact Lens as Drug Delivery System for Glaucoma Treatment: A Review

“…More than 90% of ophthalmic formulations available on the market are in the form of eye drops or ointments, indicating that topical administration is the preferred means of administration. According to a recent survey, the global ocular drug technology market was valued at $29.2 billion in 2016, and it is predicted to grow to $42.7 billion by 2023 [4]. Intraocular pressure (IOP) is a key risk factor for the disease, and eye drops are the first-line treatment for lowering it when it becomes elevated.…”