Abstract
Liposomes are small artificial vesicles spherical shaped of 50-1000 nm in diameter. They are created from natural non-toxic phospholipids membranes. Externally, they are decorated with biocompatible polymers. Chitosan, a natural polymer, demonstrates exceptional advantages in drug delivery, in particular, as liposome cover. In this paper, Molecular Dynamics simulations (MD) are performed in the coupled NPT-NPH and NVT-NVE statistical ensembles to study the static and dynamic properties of DPPC membrane-bilayer with grafted cationic chitosan chains, with added Cl(-) anions to neutralize the environment, using the Martini coarse-grained force-field. From the NPT-NPH MD simulations we found a chitosan layer L (DM) ranging from 3.2 to 6.6 nm for graft chains of a degree of polymerization n (p) = 45 and different grafting molar fractions X (p) = 0.005, X (p) = 0.014 and X (p) = 0.1. Also, the chitosan chains showed three essential grafting regimes: mushroom, critic, and brush depending on X (p). The DPPC bilayer thickness D (B) and the area per lipid A (l) increased proportionally to X (p). From the NVT-NVE MD simulations, the analysis of the radial distribution function showed that the increase of X (p) gives a more close-packed and rigid liposome. The analysis of the mean square displacement revealed that the diffusion of lipids is anomalous. In contrast, the diffusion of chitosan chains showed a normal diffusion, just after 100 ps. The diffusion regime of ions is found to be normal and independent of time. For the three identified regimes, the chitosan showed a tendency to adhere to the membrane surface and therefore affect the properties of the liposomal membrane.