1. Reactive Oxygen Species Responsive Supramolecular Prodrug Eyedrops for the Treatment of Choroidal Neovascularization.
- Author
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Xu S, Li J, Long K, and Wang W
- Subjects
- Animals, Mice, Angiogenesis Inhibitors pharmacology, Angiogenesis Inhibitors chemistry, Angiogenesis Inhibitors therapeutic use, Angiogenesis Inhibitors administration & dosage, Angiogenesis Inhibitors pharmacokinetics, Humans, Disease Models, Animal, Cyclodextrins chemistry, Polyethylene Glycols chemistry, Choroidal Neovascularization drug therapy, Choroidal Neovascularization pathology, Prodrugs chemistry, Prodrugs pharmacology, Prodrugs therapeutic use, Reactive Oxygen Species metabolism, Ophthalmic Solutions administration & dosage, Ophthalmic Solutions pharmacology
- Abstract
Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.
- Published
- 2024
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