Anti-VEGFR2 Antibody-modified Micelle for Triggered Drug Delivery and Effective Therapy of Choroidal Neovascularization

  • Curr Neurovasc Res. 2019;16(3):258-265. doi: 10.2174/1567202616666190619150956.
Kei Takahashi  1 ,  Tomomi Masuda  1 ,  Mitsunori Harada  2 ,  Tadashi Inoue  2 ,  Shinsuke Nakamura  1 ,  Kenichiro Naito  2 ,  Hideaki Hara  1 ,  Masamitsu Shimazawa  1
Affiliations
  • 1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu 501-1196, Japan.
  • 2. NanoCarrier Co., Ltd., Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba 277-0871, Japan.
PMID: 31258081 DOI: 10.2174/1567202616666190619150956
Abstract

Objective: This study aimed to examine whether DC101 (anti-VEGFR2 antibody)- modified micelles have applications as novel drug delivery devices, which allow small molecule antiangiogenic agents to deliver to angiogenic sites on a murine laser-induced choroidal neovascularization (CNV) model.

Materials and methods: CNV was induced by photocoagulation on the unilateral eye of each mouse under anesthesia. Immediately after laser coagulation, E7974-loaded DC101-modified micelles and motesanib-loaded DC101-modified micelles were intravitreally administrated. Two weeks after photocoagulation, CNV was visualized using fluorescein-conjugated dextran (MW=2,000 kDa), and the CNV area was measured in retinal pigment epithelium (RPE)-choroidal flat mounts.

Results: Intravitreal administration of both DC101-modified micelles loaded with E7974 at 2 µM and motesanib at 2 µM significantly reduced CNV area in the murine laser-induced CNV model at a clearly lower concentration than the effective dose of each agent.

Conclusion: These results suggest that DC101-modified micelle might be effective drug carrier system for treating CNV and Other ocular angiogenic diseases.

Keywords
Age-related macular degeneration; E7974; antibody-modified micelle; choroidal neovascularization; drug delivery system; motesanib..
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