Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size
Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size
复制标题
自组装纳米药物在大鼠急性肢体缺血模型中的靶向能力受尺寸影响
DOI：
10.1016/j.jconrel.2018.07.049
复制
发表时间：
2018
影响因子：
10.8
通讯作者：
Hoshina Katsuyuki
中科院分区：
文献类型：
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作者：
Suhara Masamitsu;Miura Yutaka;Cabral Horacio;Akagi Daisuke;Anraku Yasutaka;Kishimura Akihiro;Sano Masaya;Miyazaki Takuya;Nakamura Noriko;Nishiyama Ayako;Kataoka Kazunori;Koyama Hiroyuki;Hoshina Katsuyuki
外周动脉疾病（peripheral artery disease，PAD）是世界范围内最常见的疾病之一。治疗策略仅限于晚期慢性PAD或急性肢体缺血的外科或血管内手术，尚未实现预防慢性PAD恶化或再生急性肢体缺血组织的药理学方法。因此，临床上迫切需要改进治疗策略。本研究采用大鼠急性后肢缺血模型，观察药物缓释系统在预防PAD中的应用。通过使用不同尺寸的纳米药物类似物，直径为30 nm的聚离子复合物（PIC）胶束和直径为100和200 nm的PIC囊泡（PIC分别为-30，-100，-200）的比较实验，我们发现了侧支动脉中的尺寸依赖性积聚和保留。与PIC-30和-200相反，组织学分析显示PIC-100围绕小动脉并且与巨噬细胞共定位，这表明PIC-100可以实现与吞噬细胞的适度相互作用。我们的数据表明，控制纳米药物的大小有望开发新的血管生成治疗方法，以有效管理侧支动脉。
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.