Colloidal Stability of Chitosan/DNA Polyelectrolyte Complexes in Presence of Biological Polyanions

Abstract Natural or synthetic polycations are used in nucleic acid‐based therapies as complexing agents which interact electrostatically with nucleic acids, condense them into nanoparticles, protect them and control their entry into cells. However, although the literature on the formation of nanoparticles known as complexes is well documented, fewer studies have focused on the physical chemistry behind their disassembly, especially under physicochemical conditions found in an intracellular environment. There are several theories of the disassembly of these complexes, one of them consisting in the exchange between the polycations of these particles with biological polyanions. This project is focused on the study of the complexation mechanism of chitosan and calf‐thymus DNA, as well as the stability of the obtained complexes in presence of biological polyanions, i.e., glycosaminoglycans (GAGs). In the presence of polyelectrolyte complexes, GAGs that are present in cells are expected to compete with nucleic acids and dissociate the complex if polycation–GAG association is thermodynamically favored. It is found that chitosan/DNA complexes colloidal stability depends on its [N + ]/[P − ] charge ratio ( R ). Furthermore, it is determined that the aggregation onset of the complexes, generated by the addition of different GAGs, depends on the structure and the charge density of the GAGs.