상위피인용논문
서울대학교
Abstract
Young Hyo Kim, Se Hoon Gihm , and Chong Rae Park *
Enviro-Polymers Design Laboratory, Hyperstructured Organic Materials Research Center (HOMRC) and School of Materials Science and Engineering, Seoul National University, Seoul 151-744, Korea
Kuen Yong Lee ,† Tae Woo Kim , Ick Chan Kwon , Hesson Chung , and Seo Young Jeong
Biomedical Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea
* To whom correspondence should be addressed.
† Present address: Departments of Biologic & Materials Sciences and Chemical Engineering, University of Michigan, Ann Arbor, MI 48109.
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.
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