LAUSR

Abstract The use of liposomes and polyelectrolytes is on scientific and technologic scrutiny for development of gene nano carriers. We produced a reverse phase lipid:chitosan “chitosome” to which plasmid DNA (pDNA) effectively interacts and compacts. Dynamic light scattering and zeta potential evidence the complexation between pDNA and lipid:chitosan particles with size increase and surface charge decrease with concentration of plasmid. Zeta potential shows a variation of −4 mV/μg plasmid. Cell culture media have weak or even absent effect on size and surface charge of the composite complexes denoting physical stability in application media. SAXS results show increased structural organization of the lipopolyplex, with a membrane repeat distance of 6.50 nm, and gel electrophoresis confirms effective interaction between chitosomes and pDNA. The thermodynamic energy involved in complexation provides 0.29 chitosan protonated monomers interacting to phosphate group of pDNA at saturation as determined by isothermal titration calorimetry, which is in accordance with the linear charge density between chitosan and DNA. The strong exothermic binding determines Gibbs energy around −13.45 kcal/mol of protonated chitosan denoting that the complex formation leads to a state of lower Gibbs energy, thus energetically favored with decrease in entropy, corroborating compaction of plasmid chains over surface of chitosomes. A model of the lipopolyplex is unveiled thanks to the complete physicochemical description. The results demonstrate perspectives for development of a promising gene deliver.