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

J Control Release. 2015 Feb 28:200:71-7. doi: 10.1016/j.jconrel.2015.01.001. Epub 2015 Jan 5.

Abstract

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.

Keywords: Anti-angiogenic; Light-triggered; Nanoparticle; Ocular; Polymer; Triggered release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Cell Line
  • Cell Survival
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / radiation effects
  • Drug Delivery Systems*
  • Eye / metabolism
  • Indoles / administration & dosage*
  • Lactic Acid / chemistry
  • Light
  • Male
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / radiation effects*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Sprague-Dawley

Substances

  • Angiogenesis Inhibitors
  • Delayed-Action Preparations
  • Indoles
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • nintedanib