title: Combination of anti-hypertensive drugs: a molecular dynamics simulation study.
abstract: The anti-hypertensive drugs amlodipine, atenolol and lisinopril, in ordinary and PEGylated forms, with different combined-ratios, were studied by molecular dynamics simulations using GROMACS software. Twenty simulation systems were designed to evaluate the interactions of drug mixtures with a dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane, in the presence of water molecules. In the course of simulations, various properties of the systems were investigated, including drug location, diffusion and mass distribution in the membrane; drug orientation; the lipid chain disorder as a result of drug penetration into the DMPC membrane; the number of hydrogen bonds; and drug surface area. According to the results obtained, combined drugs penetrate deeper into the DMPC lipid bilayer membrane, and the lipid chains remain ordered. Also, the combined PEGylated drugs, at a combination ratio of 1:1:1, enhance drug penetration into the DMPC membrane, reduce drug agglomeration, orient the drug in a proper angle for easy penetration into the membrane, and decrease undesirable lipotoxicity due to distorted membrane self-assembly and thickness. Graphical abstract ᅟ.
authors.affiliation: Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, 15875-4413, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Yousefpour
authors.affiliation: Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, 15875-4413, Iran. hmodares@aut.ac.ir.
authors.forename: Hamid
authors.initials: H
authors.lastname: Modarress
authors.affiliation: Department of Polymer Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Goharpey
authors.affiliation: Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, 15875-4413, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Amjad-Iranagh
mesh_terms: D017311:Amlodipine / Q000737:chemistry* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000627:therapeutic use; D001262:Atenolol / Q000737:chemistry* / Q000627:therapeutic use; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D008051:Lipid Bilayers / Q000737:chemistry; D017706:Lisinopril / Q000737:chemistry* / Q000627:therapeutic use; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012984:Software; D014867:Water / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D008051:Lipid Bilayers; D014867:Water; D017311:Amlodipine; D001262:Atenolol; D017706:Lisinopril; D004134:Dimyristoylphosphatidylcholine
keywords: Anti-hypertensive drugs; Combination ratio; Combined drugs; Molecular dynamics; PEGylation