cR10-modified lenvatinib liposomes topically suppress choroidal neovascularization and improve posterior ocular drug delivery

Treating Choroidal Neovascularization (CNV), a key pathology in retinal diseases like exudative age-related macular degeneration (AMD), is challenging due to physiological barriers limiting drug delivery to the posterior eye. Current anti-vascular endothelial growth factor (VEGF) therapies, while effective, require invasive intravitreal injections, posing significant patient burden and potential complications. Lenvatinib, a potent multi-targeted tyrosine kinase inhibitor, offers strong anti-angiogenic activity, but its poor aqueous solubility and limited ocular bioavailability restrict its use. Developing a non-invasive, efficient delivery system for such compounds is crucial to overcome these limitations.

Researchers developed cR10-modified lenvatinib-loaded liposomes (cR10-LL) for enhanced topical ocular delivery. They characterized the physicochemical properties, encapsulation efficiency, and stability of the formulation. In vitro, they assessed cellular uptake and inhibitory effects on endothelial cell migration and tube formation. For in vivo evaluation, a choroidal neovascularization animal model was used, where cR10-LL was administered topically. Primary endpoints included suppression of neovascular lesion formation and reduction of vascular leakage. Ocular distribution studies confirmed drug penetration, and biocompatibility assessments evaluated safety.

The cR10 modification significantly enhanced cellular uptake of lenvatinib in vitro, leading to improved inhibitory effects on endothelial cell migration and tube formation, crucial steps in angiogenesis. In the animal model, topical administration of cR10-LL effectively suppressed neovascular lesion formation, demonstrating its therapeutic potential. Furthermore, the formulation reduced vascular leakage, a key indicator of CNV activity. Ocular distribution studies confirmed improved drug penetration into posterior ocular tissues, overcoming a major challenge for topical treatments. Biocompatibility assessments indicated favorable safety, suggesting the formulation is well-tolerated. This non-invasive approach offers a compelling alternative to current invasive therapies. > Topical cR10-LL administration effectively suppressed neovascular lesion formation and reduced vascular leakage in a choroidal neovascularization animal model.