Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye

 

Viet Anh Nguyen Huu, Jing Luo, Jie Zhu, Jing Zhu, Sherrina Patel, Alexander Boone, Enas Mahmoud, Cathryn McFearin, Jason Olejniczak, Caroline de Gracia Lux, Jacques Lux, Nadezda Fomina, Michelle Huynh, Kang Zhang, Adah Almutairi. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. J Controlled Release 2015; 200: 71-77.

 

Therapies for macular degeneration and diabetic retinopathy require intravitreal injections every 4–8 weeks. Injections are uncomfortable, time-consuming, and carry risks of infection and retinal damage. However, drug delivery via noninvasive methods to the posterior segment of the eye has been a major challenge due to the eye's unique anatomy and physiology. Here we present a novel nanoparticle depot platform for on-demand drug delivery using a far ultraviolet (UV) light-degradable polymer, which allows noninvasively triggered drug release using brief, low-power light exposure. Nanoparticles stably retain encapsulated molecules in the vitreous, and can release cargo in response to UV exposure up to 30 weeks post-injection. Light-triggered release of nintedanib (BIBF 1120), a small molecule angiogenesis inhibitor, 10 weeks post-injection suppresses choroidal neovascularization (CNV) in rats. Light-sensitive nanoparticles are biocompatible and cause no adverse effects on the eye as assessed by electroretinograms (ERG), corneal and retinal tomography, and histology.