Diffusional interaction behavior of NSAIDs in lipid bilayer membrane using molecular dynamics (MD) simulation: Aspirin and Ibuprofen

Abstract

In this research, for the first time, molecular dynamics (MD) method was used to simulate aspirin and ibuprofen at various concentrations and in neutral and charged states. Effects of the concentration (dosage), charge state, and existence of an integral protein in the membrane on the diffusion rate of drug molecules into lipid bilayer membrane were investigated on 11 systems, for which the parameters indicating diffusion rate and those affecting the rate were evaluated. Considering the diffusion rate, a suitable score was assigned to each system, based on which, analysis of variance (ANOVA) was performed. By calculating the effect size of the indicative parameters and total scores, an optimum system with the highest diffusion rate was determined. Consequently, diffusion rate controlling parameters were obtained: the drug–water hydrogen bond in protein-free systems and protein–drug hydrogen bond in the systems containing protein.

Keywords:

• non-steroidal anti-inflammatory drugs (NSAIDs)
• lipid bilayer membrane
• molecular dynamics simulation
• diffusion
• drug concentration

Acknowledgements

The authors would like to thank the Modeling and Simulation Laboratory (Supercomputer Center) at Amirkabir University for providing the required facilities to run this project.