title: Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye.
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.
authors.affiliation: Department of Nanoengineering, University of California, San Diego, United States; Department of Material Sciences and Engineering, University of California, San Diego, United States.
authors.forename: Viet Anh Nguyen
authors.initials: VA
authors.lastname: Huu
authors.affiliation: Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, United States.
authors.forename: Sherrina
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Bioengineering, University of California, San Diego, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Boone
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Enas
authors.initials: E
authors.lastname: Mahmoud
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Cathryn
authors.initials: C
authors.lastname: McFearin
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Olejniczak
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Caroline
authors.initials: C
authors.lastname: de Gracia Lux
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lux
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Fomina
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Huynh
authors.affiliation: Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, United States; KACST-UCSD Center of Excellence in Nanomedicine, University of California, San Diego, United States.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Nanoengineering, University of California, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States; Department of Chemistry and Biochemistry, University of California, San Diego, United States; Department of Material Sciences and Engineering, University of California, San Diego, United States; KACST-UCSD Center of Excellence in Nanomedicine, University of California, San Diego, United States. Electronic address: aalmutairi@ucsd.edu.
authors.forename: Adah
authors.initials: A
authors.lastname: Almutairi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000528:radiation effects; D016503:Drug Delivery Systems; D005123:Eye / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry; D008027:Light; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000528:radiation effects*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D007211:Indoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C530716:nintedanib
keywords: Anti-angiogenic; Light-triggered; Nanoparticle; Ocular; Polymer; Triggered release