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.
引用
收藏
页码:1 / 9
页数:9
相关论文
共 32 条
[1]   Thiolated chitosans [J].
Bernkop-Schnürch, A ;
Hornof, M ;
Guggi, D .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2004, 57 (01) :9-17
[2]   Development of controlled drug release systems based on thiolated polymers [J].
Bernkop-Schnürch, A ;
Scholler, S ;
Biebel, RG .
JOURNAL OF CONTROLLED RELEASE, 2000, 66 (01) :39-48
[3]   Thiolation of polycarbophil enhances its inhibition of intestinal brush border membrane bound aminopeptidase N [J].
Bernkop-Schnürch, A ;
Zarti, H ;
Walker, GF .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2001, 90 (11) :1907-1914
[4]   Thiolated polymers:: synthesis and in vitro evaluation of polymer-cysteamine conjugates [J].
Bernkop-Schnürch, A ;
Clausen, AE ;
Hnatyszyn, M .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2001, 226 (1-2) :185-194
[6]   Preparation of coated nanoparticles for a new mucosal vaccine delivery system [J].
Borges, O ;
Borchard, G ;
Verhoef, JC ;
de Sousa, A ;
Junginger, HE .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2005, 299 (1-2) :155-166
[7]   The role of glutathione in the permeation enhancing effect of thiolated polymers [J].
Clausen, AE ;
Kast, CE ;
Bernkop-Schnürch, A .
PHARMACEUTICAL RESEARCH, 2002, 19 (05) :602-608
[8]   DNases and apoptosis [J].
Counis, MF ;
Torriglia, A .
BIOCHEMISTRY AND CELL BIOLOGY, 2000, 78 (04) :405-414
[9]   Interactions of phospholipid bilayer with chitosan: effect of molecular weight and pH [J].
Fang, N ;
Chan, V ;
Mao, HQ ;
Leong, KW .
BIOMACROMOLECULES, 2001, 2 (04) :1161-1168
[10]   Asymmetrical flow field-flow fractionation and multiangle light scattering for analysis of gelatin nanoparticle drug carrier systems [J].
Fraunhofer, W ;
Winter, G ;
Coester, C .
ANALYTICAL CHEMISTRY, 2004, 76 (07) :1909-1920