Journal
BIOMATERIALS
Volume 28, Issue 3, Pages 524-531Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2006.08.017
Keywords
thiomer; chitosan-thiobutylamidine; gene delivery; nanoparticles; vector
Ask authors/readers for more resources
Chitosan-thiobutylamidine was developed and evaluated as a novel tool for gene delivery. The conjugate, displaying 299.1 +/- 11.5 mu mol free thiol groups per gram polymer, formed coacervates with pDNA at a mean size of 125 nm and a zeta potential of + 9 mV. Thiol groups, being susceptible for oxidation, were immobilised on the polymeric backbone of chitosan in order to introduce the property of extracellular stability and intracellular pDNA release by forming reversible disulfide bonds. The integrity of the new particles was compared to unmodified chitosan under simulated physiological conditions. Within 10h, pDNA was completely released from chitosan-DNA particles while only 12% were released from the thiomer-based particles. At pH 7, the amount of thiol groups significantly (p < 0.05) decreased by more than 25% within 6h. In contrast, in a reducing environment as found intracellularly, chitosanthiobutylamidine-DNA nanoparticles dissociated continuously, liberating approximately 50% of pDNA within 3 h. Transfection studies performed in a Caco2 cell culture evinced the highest efficiency for chitosan-thiobutylamidine-DNA nanoparticles in combination with a glycerol shock solution. The combination of improved stability, enhanced pDNA release under reducing conditions, and higher transfection efficiency identifies chitosan-thiobutylamidine as a promising new vector for gene delivery. (c) 2006 Published by Elsevier Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available