Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA

Sang Myoung Noh, Myung Ok Park, Gayong Shim, Su Eun Han, Han Young Lee, Jun Hyuk Huh, Myoung Suk Kim, Jin Joo Choi, Kwangmeyung Kim, Ick Chan Kwon, Jin Seok Kim, Kwang Hyun Baek, Yu Kyoung Oh

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Abstract

For delivery of siRNA, chitosan (CS) was derivatized with poly-l-arginine (PLR) and polyethylene glycol (PEG). The formation of polyplexes with siRNA was confirmed by gel retardation. The PLR-grafted CS formed nanosized particles with siRNA. PLR-grafted CS showed higher cellular delivery efficiency of siRNA than did CS, pegylated CS, PLR, or pegylated PLR. The extent of reduction in the expression of fluorescent proteins was highest following treatment of the cells using PLR derivatives of CS in complexes with specific siRNAs. Cell viability was greater in populations treated with pegylated CS-PLR than in those treated with PLR. Hemolysis of erythrocytes was reduced upon conjugation of PLR with CS. The delivery of siRNAs via pegylated CS-PLR revealed little dependence on serum. Molecular imaging techniques revealed that the intratumoral administration of red fluorescent protein-specific siRNA in complexes with pegylated CS-PLR significantly silenced the expression of red fluorescent proteins in tumor tissues in vivo. These results indicate that pegylated CS-PLR might be useful for in vivo delivery of therapeutic siRNAs.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalJournal of Controlled Release
Volume145
Issue number2
DOIs
Publication statusPublished - 2010 Jul

Keywords

  • Chitosan
  • Polyarginine
  • Polyethylene glycol
  • Serum stability
  • SiRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Noh, S. M., Park, M. O., Shim, G., Han, S. E., Lee, H. Y., Huh, J. H., Kim, M. S., Choi, J. J., Kim, K., Kwon, I. C., Kim, J. S., Baek, K. H., & Oh, Y. K. (2010). Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA. Journal of Controlled Release, 145(2), 159-164. https://doi.org/10.1016/j.jconrel.2010.04.005