Document Detail


Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life.
MedLine Citation:
PMID:  17583369     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ayumi Sato; Sung Won Choi; Miwa Hirai; Asako Yamayoshi; Rui Moriyama; Takeshi Yamano; Motoki Takagi; Arihiro Kano; Akira Shimamoto; Atsushi Maruyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-03
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  122     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-21     Completed Date:  2007-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  209-16     Citation Subset:  IM    
Affiliation:
GeneCare Research Institute Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dextrans / chemistry*
Drug Carriers / chemistry*
Drug Stability
Half-Life
Injections, Intravenous
Male
Mice
Mice, Inbred ICR
Polyethylene Glycols / chemistry*
Polylysine / analogs & derivatives*,  chemistry
RNA, Small Interfering / administration & dosage*,  blood,  pharmacokinetics*
Solubility
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Polyethylene Glycols; 0/RNA, Small Interfering; 0/poly(lysine)-graft-dextran; 0/polylysine-graft-(poly(ethylene glycol)); 25104-18-1/Polylysine; 9004-54-0/Dextrans

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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