Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells

• DOI: 10.3400/avd.ra.19-00130
• Publication Date: 2020-03-10T22:06:54Z
• Authors: Takuya Matsumoto; Sho Yamashita; Shinichiro Yoshino; Shun Kurose; Koichi Morisaki; Kaku Nakano; Jun-ichiro Koga; Tadashi Furuyama; Masaki Mori; Kensuke Egashira
• Keywords: Therapeutic angiogenesis; Arteriogenesis; Critical limb ischemia; PLGA

Two decades have passed since therapeutic angiogenesis was proposed to promote reparative collateral growth as an alternative therapy for ischemic diseases in patients whom neither surgical revascularization nor endovascular suitable. When first began, local administration conducted using recombinant factor proteins or gene-encoding factors endothelial cells. Since then, autologous stem cells and progenitor cell transplantation been developed. Although many clinical trials performed on patients, most therapies not yet become standard treatments. We developed a nanoparticle (NP)-mediated, drug-targeting delivery system bioabsorbable poly-lactic/glycolic acid (PLGA) NPs. In several animal models, pitavastatin-incorporated (Pitava)-NPs showed significant effects critical limb ischemia. Because PLGA NPs are delivered selectively vascular after intramuscular administration, it is suggested that angiogenesis/arteriogenesis plays important role the mechanism by which Pitava-NPs exert beneficial effects. To translate this medicine, we studies produced compliance with good laboratory practice/good manufacturing practice regulations, completed phase I/II trial, reporting safety efficacy of Pitava-NP injection This review will focus peripheral arterial disease induced Pitava-NPs.