Investigation Of The Interaction Between Polymyxin B Sulfate And Phosphatide By Electrochemistry

This paper briefly introduces the basic concepts of the biofilm, the basic structure of membrane molecules, membrane composition, and several models of biofilm. Biofilm structure is the basic form of cell structure, and the biofilm take part in many important processes in biology. Cell membrane isthefirst barrier to drug, so the study of the interaction of drugs and biofilm is beneficial for understanding of the drug in the body's absorption, distribution, and bioavai I ability and so on. The biofilm structure, composition and the membrane environment are very complex, so many of the current study can not be carried out in situ in the membrane. In order to facilitate the biofilm-depth study, in laboratory, researchers often prepare various smulation biomimetic membranes which often composed of one or several kinds of lipids and carry various studies for that. In this paper, several biofilm model systems have been studied by cyclic voltammetry, electrochemical impedance spectroscopy and Langmuir-Blodgett (LB) technique. That will be very useful for understanding the drug targets, new drug design, and its optimization and so on. The major elements are as follows:1. In this part, the electrochemical behavior of bilayer thiol-lipid membrances (HDM-DMPC) on gold electrode interacted with polymyxin B sulfate was investigated using cyclic voltammetry(CV) and electrochemical impedance spectroscopy(EIS).Experimental results show that polymyxin B sulfate can disrupt the orderly arrangement of phospholipid molecules and induce pores or defects on mixed bilayers, and resulting in hybrid bilayer membrane resistance decreased. Firstly, the interaction depends on time, concentration of polymyxin B sulfate, pH and cholesterol; secondarily, the self-repaired experiment shows that the defective mixed bilayers after interaction can be re-self-assembly in the KCI solution, and the extent of this self-repair and repair time relate to the concentration of polymyxin B sulfate which interact with mixed bilayers; thirdly, the investigation of their interaction using probes bearing different charge shows that the pores in the mixed bi layers are no charge selective, but the through intensity of ions inside or outside membrane may be related to electrical properties of drug.2. The interaction of polymyxin B sulfate with phosphatidylserine was investigated by electrochemical and Langmuir-Blodgett (LB) techniques in this part. Firstly, we studied the influce of polymyxin B sulfate on bilayer lipid membrances (DPPTE-DMPS) by cyclic voltammetry (CV); secondarily, the interaction of polymyxin B sulfate with phosphatidylserine (DM PS) monolayer was investigated by Langmuir-Blodgett (LB) techniques.Electrochemical experiments show that polymyxin B sulfate can decrease the orderliness of phospholipid molecules and induce pores or defects on bilayer lipid membrances, and resulting in bilayer lipid membrances resistance decreased. Firstly, molecular interactions between polymyxin B sulfate and phospholipids bilayer membranes depend on time, concentration of polymyxin B sulfate and the effect of cholesterol content in membrane; secondarily, to a certain extent, the self-repared experiment shows that the defective bilayer lipid membrances after interaction can be re-self-assembly on the surface of gold electrode at room temperature, and the extent of this self-repair and repair time relate to the concentration of polymyxin B sulfate which interact with phospholipids bilayer membranes; moreover, the investigation of their interaction with different kinds of probes shows that the through intensity of ions inside or outside membrane may be related to electrical properties of drug and membrane.LB experiment shows that lipophilic chain of polymyxin B sulfate can be embedded intothehydrophobicalkyl chain region of the DM PS, and the electrostatic interaction can combine the positively charged polymyxin B sulfate with negatively charged phosphatidylserine, thus disrupt the orderly arrangement of phosphatidylserine (DMPS) monolayer and changes molecules surface pressure caused.3. This section studied the effect of different phosphatides upon the interaction between polymyxin B sulfate and biofilm by means of cyclic voltammetry(CV).Research results show that:①regardless of the difference in molecular structure of the headgroups and lipid chains the polymyxin B sulfate can change the structure and the property of the phospholipids bilayer membranes, and consequently makes the membrane permeable. Besides, the destructiveness is proportional to the concentration of the polymyxin B sulfate;③lnvestigation the effects of lipids headgroup types on molecular interactions between polymyxin B sulfate and phospholipids, the study found that the destructiveness decreased in the sequence DMPC>DMR>DMPE;③when the phospholipids have the same headgroup, the polymyxin B sulfate interacts more readily with phospholipids containing short and unsaturated chain.