| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-01-25 |
| タイトル |
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タイトル |
Size-tunable PEG-grafted copolymers as a polymeric nanoruler for passive targeting muscle tissues. |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Mitsuru Naito
Yusuke Watanuki
Kazuko Toh
Jongmin Yum
Beob Soo Kim
Kaori Taniwaki
Satomi Ogura
Hiroki Ishida
Masaru Cho
Hiroyuki Chaya
Ken Miyajima
Yuichi Yamasaki
Kensuke Osada
Katsura Minegishi
Yoshitsugu Aoki
Kanjiro Miyata
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Muscle-targeted drug delivery is a major challenge in nanomedicine. The extravasation of nanomedicines (or nanoparticles) from the bloodstream into muscle tissues is hindered by the continuous endothelium, the so-called blood-muscle barrier. This study aimed to evaluate the optimal size of macromolecular drugs for extravasation (or passive targeting) into muscle tissues. We constructed a size-tunable polymeric delivery platform as a polymeric nanoruler by grafting poly(ethylene glycol)s (PEGs) onto the poly(aspartic acid) (PAsp) backbone. A series of PEG-grafted copolymers (gPEGs) with a narrow size distribution between 11 and 32?nm in hydrodynamic diameter (D) were prepared by changing the molecular weight of the PEGs. Biodistribution analyses revealed that accumulation amounts of gPEGs in the muscle tissues of normal mice tended to decrease above their size of ~15?nm (or?~11?nm for the heart). The gPEGs accumulated in the skeletal muscles of Duchenne muscular dystrophy model mice (mdx mice) at a 2-3-fold higher level than in the skeletal muscles of normal mice. At the same time, there was a reduced accumulation of gPEGs in the spleen and liver. Intravital confocal laser scanning microscopy and immunohistochemical analysis showed extravasation and locally enhanced accumulation of gPEGs in the skeletal muscle of mdx mice. This study outlined the pivotal role of macromolecular drug size in muscle-targeted drug delivery and demonstrated the enhanced permeability of 11-32?nm-sized macromolecular drugs in mdx mice. |
| 書誌情報 |
Journal of controlled release : official journal of the Controlled Release Society
巻 347,
p. 607-614,
発行日 2022-07
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| 出版者 |
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出版者 |
Elsevier |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1873-4995 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
35613686 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1016/j.jconrel.2022.05.030 |
