Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier

Hyo Kim Young Hyo Kim, Hoon Gihm Se Hoon Gihm, Rae Park Chong Rae Park, Yong Lee Kuen Yong Lee, Woo Kim Tae Woo Kim, Chan Kwon Ick Chan Kwon, Chung Hesson Chung, Young Jeong Seo Young Jeong

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201 Citations (Scopus)

Abstract

Precise control of the size and structure is one critical design parameter of micellar systems for drug delivery applications. To control the size of self-aggregates, chitosan was depolymerized with various amounts of sodium nitrite, and hydrophobically modified with deoxycholic acid to form self-aggregates in aqueous media. Formation and physicochemical characteristics of size-controlled self-aggregates were investigated using dynamic light scattering, fluorescence spectroscopy, and computer simulation method. The size of self-aggregates varied in the range of 130-300 nm in diameter, and their structures were found to depend strongly on the molecular weight of chitosan ranging from 5 to 200 kDa. Due to the chain rigidity of chitosan molecule, the structure of self-aggregates was suggested to be a cylindrical bamboolike structure when the molecular weight of chitosan was larger than 40 kDa, which might form a very poor spherical form of a birdnestlike structure. To explore the potential applications of self-aggregates as a gene delivery carrier, complexes between chitosan self-aggregates and plasmid DNA were prepared and confirmed by measuring the fluorescence intensity of ethidium bromide and electrophoresis on agarose gels. The complex formation had strong dependency on the size and structure of chitosan self-aggregates and significantly influenced the transfection efficiency of COS-1 cells (up to a factor of 10). This approach to control the size and structure of chitosan-derived self-aggregates may find a wide range of applications in gene delivery as well as general drug delivery applications.

Original languageEnglish
Pages (from-to)932-938
Number of pages7
JournalBioconjugate Chemistry
Volume12
Issue number6
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Young Hyo Kim, H. K., Se Hoon Gihm, H. G., Chong Rae Park, R. P., Kuen Yong Lee, Y. L., Tae Woo Kim, W. K., Ick Chan Kwon, C. K., Hesson Chung, C., & Seo Young Jeong, Y. J. (2001). Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier. Bioconjugate Chemistry, 12(6), 932-938. https://doi.org/10.1021/bc015510c