Effect of drug amlodipine on the charged lipid bilayer cell membranes DMPS and DMPS + DMPC: a molecular dynamics simulation study.

In this work, the effects of the anti-hypertensive drug amlodipine in native and PEGylated forms on the malfunctioning of negatively charged lipid bilayer cell membranes constructed from DMPS or DMPS + DMPC were studied by molecular dynamics simulation. The obtained results indicate that amlodipine alone aggregates and as a result its diffusion into the membrane is retarded. In addition, due to their large size aggregates of the drug can damage the cell, rupturing the cell membrane. It is shown that PEGylation of amlodipine prevents this aggregation and facilitates its diffusion into the lipid membrane. The interaction of the drug with negatively charged membranes in the presence of an aqueous solution of NaCl, as the medium, is investigated and its effects on the membrane are considered by evaluating the structural properties of the membrane such as area per lipid, thickness, lipid chain order and electrostatic potential difference between bulk solution and lipid bilayer surface. The effect of these parameters on the diffusion of the drug into the cell is critically examined and discussed.