TY - JOUR
T1 - Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye
AU - Huu, Viet Anh Nguyen
AU - Luo, Jing
AU - Zhu, Jie
AU - Zhu, Jing
AU - Patel, Sherrina
AU - Boone, Alexander
AU - Mahmoud, Enas
AU - McFearin, Cathryn
AU - Olejniczak, Jason
AU - De Gracia Lux, Caroline
AU - Lux, Jacques
AU - Fomina, Nadezda
AU - Huynh, Michelle
AU - Zhang, Kang
AU - Almutairi, Adah
N1 - Funding Information:
NMR spectra were collected at the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences NMR Facility. OCT and HRT tomographs were acquired at UCSD School of Medicine Core Imaging Facility, supported by the National Eye Institute ( P30EY022589 ). This work was supported by an NIH New Innovator Award ( DP 2OD006499 ) and King Abdulaziz City for Science and Technology (through the KACST-UCSD Center for Excellence in Nanomedicine and Engineering).
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/2/28
Y1 - 2015/2/28
N2 - 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.
AB - 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.
KW - Anti-angiogenic
KW - Light-triggered
KW - Nanoparticle
KW - Ocular
KW - Polymer
KW - Triggered release
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U2 - 10.1016/j.jconrel.2015.01.001
DO - 10.1016/j.jconrel.2015.01.001
M3 - Article
C2 - 25571784
AN - SCOPUS:84920747606
SN - 0168-3659
VL - 200
SP - 71
EP - 77
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -