Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life

Ayumi Sato, Sung Won Choi, Miwa Hirai, Asako Yamayoshi, Rui Moriyama, Takeshi Yamano, Motoki Takagi, Arihiro Kano, Akira Shimamoto, Atsushi Maruyama

研究成果: Contribution to journalArticle

94 引用 (Scopus)

抜粋

Delivery systems of small interfering RNA (siRNA) are the key to siRNA therapeutic application. In this study, we prepared and evaluated a series of cationic comb-type copolymers (CCCs) possessing a polycationic backbone (less than 30 weight (wt) %) and abundant water-soluble side chains (more than 70 wt.%) as a siRNA carrier with prolonged blood circulation time. Markedly, the CCC with the higher side chain content (10 wt.% PLL and 90 wt.% PEG) showed stronger interaction with siRNA than that with the lower content (30 wt.% PLL and 70 wt.% PEG), suggesting that highly dense PEG brush reinforces interpolyelectrolyte complex between the PLL backbone and siRNA. The siRNA complexed with the CCC was resistant to nucleases in 90% plasma for 24 h in vitro. The CCC having the higher side chain content increased circulation time of siRNA in mouse bloodstream by 100-fold. Surprisingly, even when the CCC and siRNA were separately injected into mouse at 20 min interval, blood circulation of post-injected siRNA was significantly increased. These results imply that the CCC has higher selectivity in its ionic interaction with siRNA than other anionic substances in blood stream. To our knowledge, this is the first example of a polyplex carrier that prolongs blood circulation time of unmodified siRNA without resource-consuming preparation process.

元の言語英語
ページ(範囲)209-216
ページ数8
ジャーナルJournal of Controlled Release
122
発行部数3
DOI
出版物ステータス出版済み - 10 8 2007

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

フィンガープリント Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Sato, A., Choi, S. W., Hirai, M., Yamayoshi, A., Moriyama, R., Yamano, T., Takagi, M., Kano, A., Shimamoto, A., & Maruyama, A. (2007). Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life. Journal of Controlled Release, 122(3), 209-216. https://doi.org/10.1016/j.jconrel.2007.04.018