Effect Of Tetracaine Hydrochloride On Dynamic Structure Of Lipid Membrane

About 60-70% of the drugs on the market are located on the lipid membrane,and the interaction between the drug and the membrane can directly affect the body’s absorption,distribution and excretion of drugs.Therefore,fully understanding the inherent influence of drugs on lipid membranes is of great significance for the diagnosis and pathological research of related diseases.In this paper,the interaction of the local anesthetic drug tetracaine hydrochloride(TTC)with binary and ternary supporting lipid bilayers was studied using fluorescence inverted microscope,and the formation conditions of lipid rafts in the supporting lipid bilayer were explored.The results indicate that TTC interacts with the binary support lipid bilayer to increase the fluidity of the lipid chain,thereby reducing the stability of the lipid bilayer,changing the structure and solubilization of the lipid membrane.When TTC was combined with the lipid membrane,local curvature change in the bilayer was observed and bright spots were formed on the surface of the lipid membrane.As the concentration of the drug increases,flexible lipid tubules of up to 20 μm are formed on the surface of the lipid membrane.After washing with a buffer solution,microporous pores are formed on the surface of the lipid membrane.Quantitative analysis shows that membrane solubilization induced by TTC can be divided into two different stages according to the function of drug concentration: In the first stage(<800 μM),the relationship between the destruction of the lipid bilayer and the drug concentration can be fitted by the Langmuir isotherm adsorption curve;In the second stage(800 μM-25 m M),TTC solubilizes the lipid membrane in a detergent-like manner,and the relationship between the destruction of the lipid bilayer and the drug concentration is linear.Interestingly,bilayer solublization was caused by TTC below its critical micelle concentration(cmc),indicating the local accumulated of TTC in the lipid membrane.In addition,we found that the introduction of cholesterol increased the insertion of TTC in the lipid membrane,thereby promoting the solubilization of the lipid bilayer by TTC.The lipid raft is essentially the result of the coexistence of Lo and Ld in the lipid membrane,which needs to contain unsaturated phospholipids and a large amount of saturated phospholipids.The research on the ternary support lipid bilayers found that the mixed liposomes are in a homogeneous phase at room temperature,and the two phases cannot produce phase separation.Phase separation occurs only when the temperature is higher than the phase transition temperature of the mixed liposome,and a lipid raft structure appears on the lipid membrane.When 5 m M and 25 m M TTC were introduced into a lipid membrane containing 10% cholesterol,we found that the interaction of TTC with lipid bilayer is more pronounced under high concentration conditions and can induce an increase in the curvature of the lipid membrane.When the lipid membrane was completely washed with a buffer solution,the surface of the lipid membrane returned to its original state,indicating that changes in the composition of lipid membranes will affect the strength of TTC and membrane interactions,and reduce the insertion of TTC.The findings may provide new insights into the possible mechanisms of anesthetic drugs interact with lipid membranes and contribute to the rational design of more effective and less toxic therapeutic agents.