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Viet Anh Nguyen Huu, Jing Luo, Jing Zhu, Enas Mahmoud, Cathryn McFearin, Nadezhda Fomina, Kang Zhang, Adah Almutairi, ; Shining a Light on Drug Delivery: On-Demand Light-triggered Release of Payload in the Eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):442.
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Anti-VEGF therapy commonly used to treat macular degeneration and diabetic retinopathy requires intravitreal injections every 4-8 weeks. Injections are uncomfortable, time-consuming, and carry a small risk 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 platform for on-demand drug delivery using an ultraviolet (UV) light-degradable polymer, which allows for temporally-controlled, noninvasive drug release.
Nanoparticles containing a fluorescent dye as a model drug are formulated by emulsion-evaporation techniques. UV irradiation conditions are determined by examining their effects on cultured lens explants. Control over payload release upon UV irradiation is studied in vitro on various cell lines, including retinal pigment epithelium cells. Biocompatibility of the materials is tested via electroretinograms (ERG), intraocular pressure (IOP) measurements, histology, and qRT-PCR for common cytokines. Temporal control over payload release in vivo is examined in rats by fluorescent imaging of retinal flatmounts of irradiated and non-irradiated eyes at various timepoints post-injection of nanoparticles. Therapeutic potential is studied using nanoparticles containing a biologic VEGFR/PDGFR inhibitor in a laser-induced choroidal neovascularization (CNV) model.
Lens explant studies show 5 min of 365 nm UV light at 8mW/cm2 does not cause cloudiness characteristic of cataract formation. There was no significant difference in electrophysiological response, IOP, or IL1β and TNFα expression in the retinas of eyes injected with our UV-responsive particles relative to saline- or non-injected eyes at 7 days post-injection. Nanoparticles containing fluorescent dye remain intact and responsive to light up to 12 weeks post-injection.
Materials formulated in nanoparticles are safe in the eye and retain their ability to release drug upon irradiation with benign levels of UV light up to at least 12 weeks post-injection. This nanoparticle platform has the potential to deliver a variety of molecules, including small hydrophobic drugs and proteins.
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