ArticleTranslational vision science & technology2025
Carboxyamidotriazole Complexed to PLGA Is Safe, Effective, and Durable in Models of Neovascular Retinal Disease.
Article in Translational vision science & technology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: We evaluated the safety and bioactivity of carboxyamidotriazole (CAI) using two approaches, a polymeric CAI-PLGA nanoemulsion in the mouse model of choroidal neovascularization (CNV) and CAI-loaded bioresorbable intravitreal implant in a rabbit model of vascular leakage. Methods: Mice underwent laser rupture of Bruch's membrane to induce CNV followed by a single (2 µL volume) intravitreal injection of either vehicle (n = 11); CAI nanoparticles (0.5 µg, 1 µg, 2 µg, 400 nM, 800 nM, and 1.6 µM, respectively); aflibercept 10 µg; or CAI nanoparticles (1 µg) + aflibercept 10 µg. New Zealand white rabbits underwent either sham intravitreal injection, aflibercept 500 µg injection, or CAI-PLGA intravitreal implant. Vascular leakage was induced with injections of VEGF on days 23 and 53. On days 30 and 60, all groups underwent vitreous fluorophotometry and fundus imaging. On day 60, the rabbits were euthanized, and their eyes were enucleated. Results: Intravitreal injection of the CAI-Nano at the dose of 1 µg significantly decreased choroidal neovascular volume, to 25% of saline on day 7 and 30% on day 14, which was comparable to aflibercept. Vitreous fluorophotometry revealed significantly lower levels of fluorescein in the aflibercept and CAI implant groups compared to the sham group on day 30. On day 60, the CAI implant group showed significantly reduced neovascularization as compared with the aflibercept groups. No toxicity was observed in any group. Conclusions: CAI in nanoparticle formulation or as a sustained release bioresorbable implant showed potent efficacy and caused no retinal toxicity in murine and rabbit models. Translational Significance: CAI demonstrates strong potential as a sustained release anti-angiogenic therapy with effective long-term durability.
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