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

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)71-77
Number of pages7
JournalJournal of Controlled Release
Volume200
DOIs
StatePublished - Feb 28 2015

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Keywords

  • Anti-angiogenic
  • Light-triggered
  • Nanoparticle
  • Ocular
  • Polymer
  • Triggered release

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Huu, V. A. N., Luo, J., Zhu, J., Zhu, J., Patel, S., Boone, A., Mahmoud, E., McFearin, C., Olejniczak, J., De Gracia Lux, C., Lux, J., Fomina, N., Huynh, M., Zhang, K., & Almutairi, A. (2015). Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. Journal of Controlled Release, 200, 71-77. https://doi.org/10.1016/j.jconrel.2015.01.001