Stability and binding affinity of DNA/chitosan complexes by polyanion competition. (15th November 2017)

• Record Type: Journal Article
• Authors: Ma, Pei Lian; Lavertu, Marc; Winnik, Françoise M.; Buschmann, Michael D.
• Is Part Of: Carbohydrate polymers. Volume 176(2017)
• Page Start: 167
• Page End: 176
• Publication Date: 2017-11-15
• Subjects: Nanoparticle -- Polyplex -- Gene delivery -- Isothermal titration calorimetry -- Chitosan -- DNA; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2017.08.002
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Only polyanions with high charge density can disassemble DNA/chitosan complexes. Complex stability exposed to polyanion increases with chitosan DDA and chain length. Free chitosan could play an important role in preventing premature release of DNA. Abstract: The stability of DNA/chitosan complexes upon exposure to hyaluronic acid, chondroitin sulfate, and heparin, was assessed by fluorescence spectroscopy to quantify DNA release. Only the highly charged heparin was found to release DNA from the complexes. Complex stability upon exposure to heparin increased with the degree of deacetylation and molecular weight of chitosan and with the ratio of chitosan amino groups to DNA phosphate groups (N/P ratio) in the complexes. Isothermal titration microcalorimetry revealed that among polyanions tested, only heparin has a binding affinity to chitosan approaching that of DNA and can therefore release DNA from the complexes. These results also indicate that anionic components with sufficiently high charge density can induce extracellular or intracellular release of DNA, the former negatively affecting delivery efficiency while the latter is required for gene transfer to occur. Our findings also suggest that increased N/P ratio of the complexes can play an important role in preventing premature dissociation of DNA/polycation complexes upon interaction with anionic components in extracellular milieu.