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

Abstract

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.

The Signature of Fluctuations of the Hydrogen Bond Network Formed by Water Molecules in the Interfacial Layer of Anionic Lipids

“…Also, pressure isotherm studies have shown that DMPS monolayers collapse at an APL of ~0.40 nm 2 [69]. Computational studies provided estimations of 47.6 nm 2 in the gel (30 • C) and 55.6 nm 2 in the fluid phase (60 • C) for pure bilayers or ~0.60 nm 2 for bilayers containing small molecules [70]. The respective studies also provided bilayer thickness estimates of 4.0-4.4 nm, or ~3.5 nm.…”

CellSys: An open‐source tool for building initial structures for bio‐membranes and drug‐delivery systems

“…In addition, this will reduce the system generation time, for each simulation. In the following examples, some systems are studied to indicate how successfully they are built by using this package 7,9 . In performing these simulations the forcefield parameters for validation cases are obtained from Lipidbook 43 .…”

“…Also MD simulation studies have been used to elucidate the behavior of drug and drug carriers 3,4 with the phospholipid membranes as well as the mechanism involved in interaction between cell membranes, proteins and enzymes 5,6 . Besides, by analysis of the experimental and simulations it has been suggested that the structure of PLCMs in both pure and mixed forms, 7 play a critical role penetration of the drug in to the membrane 8 . In other words, the diffusion of drug or drug carrier through the membrane could be studied and analyzed using free‐energy analysis or pooling force analysis, to deduce the efficiency of the drug‐delivery system 4,9 .…”

Molecular dynamics simulation study of doxorubicin adsorption on functionalized carbon nanotubes with folic acid and tryptophan

“…In the present molecular dynamics studies 39 – 42 , the adsorption and release of DOX have been investigated for CNT, functionalized with FA and tryptophan (Trp) (a non-polar aromatic amino acid) 43 in both neutral and acidic pH.…”