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Chitosan-thioglycolic acid conjugate: An alternative carrier for oral nonviral gene delivery?
被引:61
作者:
Martien, Ronny
Loretz, Brigitta
Thaler, Marlene
Majzoob, Sayeh
Bernkop-Schnuerch, Andreas
机构:
[1] Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, 6020 Innsbruck
[2] Institute of Zoology, Leopold-Franzens-University of Innsbruck, 6020 Innsbruck
[3] Department of Pharmaceutics, Tehran University of Medical Sciences
关键词:
nonviral vector;
thiolated chitosan;
thioglycolic aid (TGA);
gene delivery;
transfection rate;
D O I:
10.1002/jbm.a.31135
中图分类号:
R318 [生物医学工程];
学科分类号:
0831 ;
摘要:
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 mined 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. (c) 2007 Wiley Periodicals, Inc.
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页码:1 / 9
页数:9
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