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

[ Vol. 16 , Issue. 3 ]

Author(s):

Kei Takahashi, Tomomi Masuda, Mitsunori Harada, Tadashi Inoue, Shinsuke Nakamura, Kenichiro Naito, Hideaki Hara and Masamitsu Shimazawa *   Pages 258 - 265 ( 8 )

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 epithelia (RPE)-choroidal flat mounts.

Results: Intravitreal administration of both DC101-modified micelle 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.

Affiliation:

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, NanoCarrier Co., Ltd., Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba 277-0871, NanoCarrier Co., Ltd., Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba 277-0871, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, NanoCarrier Co., Ltd., Chuou 144-15, 226-39 Wakashiba, Kashiwa, Chiba 277-0871, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196



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