Silicon nanoneedles for sustained treatment of choroidal angiogenesis

Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss and blindness in wet macular degeneration. To treat CNV, intravitreal anti-vascular endothelial growth factor therapy (VEGF) such as bevacizumab (BEV) are often utilized, but these treatments require frequent invasive administration and can carry a risk of eye infection. To improve the treatment efficiency, reduce the treatment burden, and reduce side-effects and invasiveness, the current study describes a novel treatment of CNV using miniature biodegradable silicon nanoneedles (SiNNs) fabricated on a tear-soluble contact lens.

Methods: The SiNNs were encapsulated with BEV (BEV@SiNNs) and used as drug carriers for long-term, sustained drug delivery. BEV@SiNNs were evaluated on a New Zealand rabbit CNV model (n = 7) after approval from the University of Michigan IACUC. To generate CNV, subretinal injection of Matrigel (20 μL) and VEGF (7.5 μL, 100 μg/mL) was performed using a 30G Hamilton needle. A contact lens was inserted subconjunctivally on the posterior sclera 3 days after CNV creation and monitored by color fundus photography, OCT, and fluorescein angiography (FA) before and at 1, 3, 7, 14, and 28 days and then monthly for up to 1 year post-treatment.

Results: BEV@SiNNs resulted in long-term, sustained reduction in mean FA CNV leakage intensity for at least 1 year. There was a rapid 45% reduction in CNV within 1 week. CNV continued to gradually reduce further to an 80% reduction in CNV by 4 months that was persistent to 12 months. Control CNV did not have a significant change in CNV over 1 year. Rabbits were comfortable on the grimace scale, and no complications occurred with treatment in any animals. OCT showed normal retinal morphology and layers.

Conclusions: SiNNs are an efficient drug delivery platform technology for long-term (at least 1 year), sustained treatment of CNV in this rabbit model.