Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier.
- Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier.
- 김영효; 김세훈; 박종래; 이근용; 김태우; 권익찬; 정혜선; 정서영
- Issue Date
- Bioconjugate chemistry
- VOL 12, NO 6, 932-938
- 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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