Journal
JOURNAL OF CONTROLLED RELEASE
Volume 286, Issue -, Pages 394-401Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2018.07.049
Keywords
Acute limb ischemia; Collateral growth; Polymeric micelles; Polymeric vesicles
Funding
- Center of Innovation (COI) Program from Japan Science and Technology Agency (JST)
- Project for Cancer Research And Therapeutic Evolution (P-CREATE) from Japan Agency for Medical Research and Development (AMED) [16cm0106202h0001]
- [24689051]
- [16H05422]
- [26462100]
- [16K10652]
- [JP16H03179]
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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.
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