Partitioning of Nonsteroidal Antiinflammatory Drugs in Lipid Membranes: A Molecular Dynamics Simulation Study

• Published in: Biophysical journal Vol. 98; no. 4; pp. 586 - 595
• Main Authors: Boggara, Mohan Babu, Krishnamoorti, Ramanan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-02-2010; Biophysical Society; The Biophysical Society
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Aspirin - chemistry; Aspirin - metabolism; Biophysics; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell Membrane Permeability; Charge; Drugs; Hydrogen Bonding; Hydrogen-Ion Concentration; Ibuprofen; Ibuprofen - chemistry; Ibuprofen - metabolism; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Liquid Crystals - chemistry; Membrane; Membranes; Molecular dynamics; Molecular Dynamics Simulation; Nonsteroidal antiinflammatory drugs; Partitioning; Simulation; Static Electricity; Steroids; Thermodynamics; Water - chemistry
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2009.10.046

Using the potential of mean constrained force method, molecular dynamics simulations with atomistic details were performed to examine the partitioning and nature of interactions of two nonsteroidal antiinflammatory drugs, namely aspirin and ibuprofen, in bilayers of dipalmitoylphosphatidylcholine. Two charge states (neutral and anionic) of the drugs were simulated to understand the effect of protonation or pH on drug partitioning. Both drugs, irrespective of their charge state, were found to have high partition coefficients in the lipid bilayer from water. However, the values and trends of the free energy change and the location of the minima in the bilayer are seen to be influenced by the drug structure and charge state. In the context of the transport of the drugs through the bilayer, the charged forms were found to permeate fully hydrated in contrast to the neutral forms that permeate unhydrated.