Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization

Adv Mater. 2024 Jun;36(23):e2314095. doi: 10.1002/adma.202314095. Epub 2024 Feb 22.

Abstract

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (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, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve 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 distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve 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 and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Keywords: age‐related macular degeneration; antiangiogenesis; anti‐inflammation; co‐assembled nanoparticles; sustained release.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Choroidal Neovascularization* / drug therapy
  • Choroidal Neovascularization* / metabolism
  • Choroidal Neovascularization* / pathology
  • Delayed-Action Preparations* / chemistry
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Liberation
  • Humans
  • Indoles* / chemistry
  • Indoles* / therapeutic use
  • Mice
  • Nanoparticles* / chemistry
  • Rabbits

Substances

  • Delayed-Action Preparations
  • Indoles
  • Angiogenesis Inhibitors
  • nintedanib
  • Drug Carriers