ArticleInternational journal of pharmaceutics: X2026
Harnessing oleic acid for facilitating topical delivery of lipid nanoparticle to the ocular posterior segment and improving anti-angiogenesis effect.
Article in International journal of pharmaceutics: X, 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
Fundus neovascularization is a leading cause of vision loss. Axitinib, a tyrosine kinase inhibitor, has significant antiangiogenic effects but suffers from extremely low aqueous solubility and faces multiple ocular barriers when topically instilled. Here, we incorporated oleic acid into a lipid nanoparticle for the topical ocular delivery of axitinib. Meanwhile, we systemically investigated the impact of oleic acid and its content on the performance of lipid nanoparticles in vitro, ex vivo, and in vivo. The lipid nanoparticle with 2% oleic acid achieved a 2125-fold increase in axitinib solubility. Pharmacokinetic analysis in rat tears showed that oleic acid did not compromise ocular retention. An ex vivo ocular tissue permeability study revealed concentration-dependent enhancement of corneal permeability and scleral retention by oleic acid. An in vivo biodistribution study indicated that oleic acid facilitated the transport of the lipid nanoparticle into the posterior segment. Consequently, compared to a lipid nanoparticle without oleic acid, this one containing 2% oleic acid showed higher drug bioavailability in posterior segment tissues and a stronger anti-angiogenesis effect in a laser-induced choroidal neovascularization animal model. In addition, the lipid nanoparticle containing 2% oleic acid level exhibited excellent ocular biocompatibility. Overall, our findings highlight the crucial role of oleic acid in non-invasive ocular drug delivery and provide valuable insights into developing fatty acid-containing topical drug delivery systems to treat fundus diseases.
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