Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size

Masamitsu Suhara, Yutaka Miura, Horacio Cabral, Daisuke Akagi, Yasutaka Anraku, Akihiro Kishimura, Masaya Sano, Takuya Miyazaki, Noriko Nakamura, Ayako Nishiyama, Kazunori Kataoka, Hiroyuki Koyama, Katsuyuki Hoshina

Research output: Contribution to journalArticle

Abstract

Peripheral artery disease (PAD) is one of the most spreading diseases all over the world. The treatment strategies are limited to surgical or endovascular procedures for final stage chronic PAD or acute limb ischemia, and no pharmacological approaches have been achieved to prevent the worsening of chronic PAD or to regenerate the tissues of acute limb ischemia. Therefore, the improvement of therapeutic strategy is strongly demanded in clinics. Here, we adopted an acute hindlimb ischemia model in rats, which provides concomitant inflammatory response, to evaluate the application of drug delivery system against PAD. Through comparative experiments by using different-sized nanomedicine analogues, polyion complex (PIC) micelles with 30 nm diameter and PIC vesicles with 100- and 200-nm diameter (PICs-30, −100, −200 respectively), we found the size-dependent accumulation and retention in the collateral arteries. In contrast to PICs-30 and -200, histological analysis showed that PICs-100 were around the arterioles and co-localized with macrophages, which indicates that the PICs-100 can achieve moderate interaction with phagocytes. Our data suggests that controlling the size of nanomedicines has promise for developing novel angiogenic treatments toward the effective management of collateral arteries.

Original languageEnglish
Pages (from-to)394-401
Number of pages8
JournalJournal of Controlled Release
Volume286
DOIs
Publication statusPublished - Sep 28 2018

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All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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