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Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system

Paper ID Volume ID Publish Year Pages File Format Full-Text
11521 746 2007 8 PDF Available
Title
Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system
Abstract

Chitosan-thiobutylamidine was developed and evaluated as a novel tool for gene delivery. The conjugate, displaying 299.1±11.5 μmol 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 10 h, 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 6 h. In contrast, in a reducing environment as found intracellularly, chitosan-thiobutylamidine–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.

Keywords
Thiomer; Chitosan-thiobutylamidine; Gene delivery; Nanoparticles; Vector
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Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 3, January 2007, Pages 524–531
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us