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Chitosan–thioglycolic acid conjugate: An alternative carrier for oral nonviral gene delivery?
Author(s) -
Martien Ronny,
Loretz Brigitta,
Thaler Marlene,
Majzoob Sayeh,
BernkopSchnürch Andreas
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31135
Subject(s) - chitosan , thioglycolic acid , gene delivery , conjugate , carbodiimide , materials science , zeta potential , cytotoxicity , nanoparticle , transfection , nuclear chemistry , nanotechnology , chemistry , biochemistry , in vitro , polymer chemistry , gene , mathematical analysis , mathematics
Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated. The aim of this study was to synthesize and evaluate a thiolated chitosan to improve the efficacy of oral gene delivery systems. Thiolated chitosan was synthesized by introducing thioglycolic acid (TGA) to chitosan via amide bond formation mediated by a carbodiimide. Based on this conjugate, nanoparticles with pDNA were generated at pH 4.0 and 5.0. Cytotoxicity of the thiolated chitosan/pDNA nanoparticles on Caco‐2 cells was evaluated. The diameter of thiolated chitosan/pDNA nanoparticles was in the range of 100–200 nm. The zeta potential was determined to be 5–6 mV. Due to stability toward nucleases, the transfection rate of thiolated chitosan/pDNA nanoparticles was fivefold higher than that of unmodified chitosan/pDNA nanoparticles. Lactate dehydrogenase tests for thiolated chitosan/pDNA (pH 4.0 and 5.0) showed that (3.79 ± 0.23)% and (2.9 ± 0.13)% cell damage. According to these results, thiolated chitosan represents promising excipients for preparation DNA nanoparticles in nonviral gene delivery system. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007