New treatment strategy for acute lower limb ischemia by using nano-micell

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10652
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: The University of Tokyo
• Principal Investigator: KOYAMA HIROYUKI 東京大学, 医学部附属病院, 登録研究員 (10241994)
• Co-Investigator(Kenkyū-buntansha): 宮原 拓也 東京大学, 医学部附属病院, 助教 (20704943) ; 三浦 裕 東京大学, 大学院工学系研究科(工学部), 客員研究員 (40557980) ; 保科 克行 東京大学, 医学部附属病院, 講師 (90571761)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Nano-micelle / ischemia

Outline of Final Research Achievements

There are many unsolved problems in angiogenesis therapy for inoperable severe peripheral artery disease. In this study, we attempted to develop a drug delivery system to the collateral circulation site by polyion complex type nanoparticles as new angiogenesis therapy. The present study revealed that precise adjustment of the particle size can control the accumulation efficiency at the target site in systemic administration. Furthermore, we succeeded in synthesizing particles containing IL-1β as a drug, which can be expected to promote collateral circulation. However, the accumulation of the particles at the target site was weak, and it was inferred that the factor is attributed to the difference in the particle stability in blood. In the future, reexamination of the molecular design of drug-containing nanoparticles and optimization of the particle adjustment conditions are desired.

Free Research Field

Vascular Surgery

Academic Significance and Societal Importance of the Research Achievements

下肢虚血に対する薬剤投与は、静脈注射での力価では毒性がでる可能性があるため、出来る限り低容量が望ましい。その点ナノミセルを用いたドラッグデリバリーでは、病変部のみに集積し、同部でreleaseされるため効率的である。ただ内包する薬剤とナノミセルとの相性があり、サイズ、電荷など、臨床応用に向けてまだハードルがある。今回の成果で、内包化の最適化が示され、今後の臨床応用への重要なデータを示すことができた。