The Effect Of Polyethyleneimine On The Structure And Properties Of Zwitterionic And Anionic Liposomes

In recent years, due to its high transfection efficiency, polyethyleneimine (PEI) becomes one of the most representative nonviral gene carriers. However, the safety issues of PEI are raised by their toxicity in clinical application, and its mechanism with cells still needs to be further explored. This paper we chose two typical phospholipid:zwitterionic soy lecithi (SPC) and anionic 1,2-dioleoyl-sn-glycerol-3-phospho-l-serine (DOPS) to prepare the liposomes (LUVs) in order to simulate cell membrane. Then researched the influence of three kinds of branched PEIs which has different molecular weight on cell membrane structure and the interaction mechanism between them from the molecular level, so as to provide a theoretical basis for the disturbance mechanism of PEI on cell membrane. The main results are as follows:For PEI-SPC LUVs system, All of the PEIs (PEI25K, PEI10K and PEI1.8K) could interact with liposomes via hydrogen bonding and Van der Walls force in a certain concentration range, then led to a complex by liposomes aggregation and resulted in the increase of particle size, accompanied a trend of surface potential from negative to positive changes. By the way, the combination of this two material was a exothermic process. At the same time, PEI could combine with quercetin(QUE)-a kind of flavonoids, and enhanced the ability of QUE to cross the bilayer’s outer leaflet in low concentration, while the membrane permeability of inner leaflet could decrease. Meanwhile, PEI could slightly increase the fluidity of bilayer’s outer leaflet, otherwise the fluidity of the inner leaflet would become smaller while the concentration continuously increased, but the overall change was not obvious. The interaction between them was also related to the molecular weight of PEI, PEI25K had the highest strength.For PEI-DOPS LUVs system, the interaction between them was stronger due to DOPS has more negative charges. Therefore, PEI could cause the fusion of these anionic liposomes in some specific concentration. The changes of zeta potential and ITC results showed that interaction between PEI and LUVs was mainly contributed by hydrogen bonding and Van der Walls force. At the same time, charge inversion of DOPS LUVs happened because of the adsorption of PEI onto the liposomes surface, the combination of them was a exothermic process as well. In this concentration window, the permeation of QUE through lipid membranes enhanced, accompanied with the decrease of membrane fluidity. Similarly, the molecular weight of PEI had an influence on their combination.Difference between the interaction of PEI-SPC LUVs and PEI-DOPS LUVs lied in whether the membrane fusion happened as well as the different influence of permeability and fluidity of lipid membrane.