Current Neurovascular Research

Author(s): Kei Takahashi, Tomomi Masuda, Mitsunori Harada, Tadashi Inoue, Shinsuke Nakamura, Kenichiro Naito, Hideaki Hara and Masamitsu Shimazawa *

DOI: 10.2174/1567202616666190619150956

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

Page: [258 - 265] Pages: 8

  • * (Excluding Mailing and Handling)

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, choroidal neovascularization, antibody-modified micelle, E7974, motesanib, drug delivery system.