ArticleInvestigative ophthalmology & visual science2026
Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration.
Article in Investigative ophthalmology & visual science, 2026. 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: In neovascular age-related macular degeneration (nAMD), invasive intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is the current standard of care, highlighting the need for noninvasive eye drop formulations. We aimed to assess the ocular pharmacokinetics and anti-angiogenic efficacy of nanocrystallized tivozanib (nTivo) eye drops in rabbits and monkeys. Methods: We investigated the ocular distribution of nTivo eye drops and conventional microcrystallized tivozanib eye drops in albino and pigmented rabbits. The anti-angiogenic efficacy of nTivo eye drops was evaluated in laser-induced choroidal neovascularization (CNV) model monkeys. Results: In pigmented rabbits, nTivo eye drops showed up to 9.5-fold higher drug delivery efficiency to the retina/choroid relative to microcrystal formulations, indicating that nanocrystallization enhances the drug delivery efficiency of tivozanib to posterior eye tissues. Additionally, accumulation of the ocular exposure was observed with the repeated instillation of nTivo eye drops, and the elimination half-life (t1/2) of tivozanib was longer in the retina/choroid (247.5 hours) than in serum (49.7 hours). In comparison to albino rabbits, pigmented rabbits showed higher exposure (3.2-fold) and longer t1/2 (5.7-fold) in the retina/choroid, suggesting that the melanin binding properties of tivozanib potentially contribute to its accumulation and prolonged retention in the retina and choroid. In the monkey CNV model, nTivo eye drops significantly reduced the neovascularization lesion area. Conclusions: The nTivo eye drop formulation may be a potential new treatment option for nAMD due to its preferable ocular pharmacokinetic and anti-angiogenic profiles based on potential contributions of nanocrystallization and the melanin binding properties of tivozanib.
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