Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multi-target Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-VEGF is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, could co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibited significantly improved stability and achieved long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distributed in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization (CNV) model, the L/N NPs after a minimally invasive subconjunctival administration could successfully inhibit angiogenesis, chronic inflammation and scavenge oxidative stress, achieved comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis, reduce inflammation, and counteract oxidative stress, holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition. This article is protected by copyright. All rights reserved.