Chitosan-induced perturbation of dipalmitoyl-sn-glycero-3-phosphocholine membrane bilayer

Recently, chitosan, a positively charged polysaccharide in slightly acidic condition, has been used as a membrane perturbant in a novel gene delivery assay. In this study, the fundamental interactions between chitosan and DPP C membrane bilayers were investigated with cross-polarization microscopy, d ifferential scanning calorimetry and Fourier transform (FT) Raman spectrosc opy. The cross-polarized images showed that chitosan induced fusions of mul tilamellar vesicles. It was determined that the mixing of chitosan with dip almitoyl-sn-glycero-3-phosphocholine (DPPC) and subsequent hydration of the mixture at 60 degreesC significantly suppressed the enthalpy of the gel-li quid crystalline transition in a concentration-dependent manner. Chitosan a lso affected the thermotropic behavior of DPPC bilayer during the cooling c ycle. However, chitosan addition to DPPC had no effect on the main phase tr ansition temperature (T,) of DPPC bilayers. When DPPC and chitosan were mix ed in chloroform before hydration, the initial rate of enthalpy reduction a gainst chitosan concentration was significantly increased. Furthermore, the dependence of the cooperative unit of the DPPCs main transition on the chi tosan mole fraction showed that chitosan tuned the intermolecular interacti ons between neighboring lipid molecules. FT-Raman spectroscopy provided sol id evidence that the attractive interchain and intermolecular forces of the hydrophobic core (acyl chains) in the DPPC bilayer were significantly redu ced by the chitosan-membrane interactions. The addition of chitosan also re duced the order in the two-dimensional packing of the acyl chains and incre ased the fluidity of the DPPC bilayer. This study provided new insights int o the physicochemical interactions between model membrane and chitosan that might aid the development of a novel membrane perturbant for gene delivery .