Paper Title:
Polymer Brush-Stabilized Polyplex for a siRNA Carrier with Long Blood Circulatory Half-Life
  Abstract

Small interfering RNA (siRNA) holds potential as a therapeutic approach to silence targeted gene of disease, but siRNA has limited stability in vivo. Therefore, delivery system of siRNA is the key to siRNA therapeutic application. We attempted to develop a delivery system, which enables siRNA to demonstrate high stability and long blood circulation. We synthesized a series of bottlebrush-type copolymers (BBCs) possessing polycationic backbone (less than 30 wt%) and abundant water-soluble side chains (more than 70 wt%) as siRNA carrier. A siRNA complexed with the BBC was resistant to nuclease and stable in plasma. Especially, the BBC (10 wt% PLL and 90 wt% PEG) having higher grafting ratio (≈ 90 wt%) of water-soluble side chains showed 100-times enhanced stability of siRNA in mouse bloodstream in vivo. Surprisingly, even when the BBC and siRNA separately injected into mouse at 20 min interval, the BBC increased blood half life of the siRNA. These results suggest that the BBC has higher selectivity in its ionic interaction to siRNA than other anionic substance in blood components. To our knowledge, this is the first report of siRNA delivery carrier which prolonged blood circulation of siRNA without resource-consuming preparation process.

  Info
Periodical
Advanced Materials Research (Volumes 47-50)
Edited by
Alan K.T. Lau, J. Lu, Vijay K. Varadan, F.K. Chang, J.P. Tu and P.M. Lam
Pages
762-764
DOI
10.4028/www.scientific.net/AMR.47-50.762
Citation
A. Kano, T. Yamano, S. W. Choi, A. Maruyama, "Polymer Brush-Stabilized Polyplex for a siRNA Carrier with Long Blood Circulatory Half-Life ", Advanced Materials Research, Vols. 47-50, pp. 762-764, 2008
Online since
June 2008
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$35.00
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