Antiangiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease

Adv Mater. 2022 Jun;34(25):e2108360. doi: 10.1002/adma.202108360. Epub 2021 Dec 2.

Abstract

The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.

Keywords: angiogenesis inhibitors; drug carriers; drug delivery systems; micelles; ophthalmic solutions; retinal diseases.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Choroidal Neovascularization* / drug therapy
  • Choroidal Neovascularization* / etiology
  • Drug Delivery Systems
  • Mice
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins
  • Retinal Diseases* / complications
  • Retinal Diseases* / drug therapy
  • Swine
  • Vascular Endothelial Growth Factor A

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor