Ocular Penetrating Carrier (OPC) eye drops deliver aflibercept, matching intravitreal injection efficacy in mouse CNV model.

Current treatments for choroidal neovascularization (CNV), a key pathology in Age-related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and Diabetic Macular Edema (DME), rely on invasive intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) drugs like aflibercept. These injections are painful, carry risks, and lead to significant patient burden, often resulting in poor adherence to chronic treatment regimens. The physiological barriers of the eye, particularly to the posterior segment, make non-invasive delivery of large molecule therapeutics exceptionally challenging, creating a critical unmet need for alternative drug delivery methods.

Researchers developed and screened modified cell penetrating peptides (CPPs) to create Ocular Penetrating Carriers (OPCs) designed for enhanced ocular penetration of large molecules. They formulated aflibercept alone or with anti-Ang2 with OPCs and applied them as eye drops to mouse eyes to measure intraocular drug levels. Penetration in larger animals was assessed by applying 50 µg eye drops to pig eyes. Efficacy was evaluated in a laser-induced CNV mouse model, where aflibercept/OPC eye drops (20 µg, five drops per day) were compared to IVT injection of aflibercept (20 µg) by measuring vascular leakage, lesion volume, and CNV area.

OPC-formulated eye drops significantly improved intraocular delivery of aflibercept, achieving up to sixfold higher levels in mouse eyes compared to a previously published CPP. In the laser-induced CNV mouse model, aflibercept/OPC eye drop treatment effectively decreased vascular leakage, lesion volume, and CNV area by 20% to 50%. This therapeutic effect was found to be similar to that achieved with intravitreal injection of aflibercept (20 µg). Intraocular penetration of select OPCs was also confirmed in pig eyes, demonstrating the carrier's ability to traverse larger animal ocular barriers. > Importantly, the study also showed that a single OPC eye drop could simultaneously deliver two different protein therapeutics into the eye, highlighting its versatility for combination therapies.