- 1:42 PM

Computational Insights into the Interaction of Non Steroidal Anti Inflammatory Drugs with Lipid Membranes

Mohan babu Boggara, University of Houston, Department of Chemical Engineering, S222 Engng Bldg 1, Houston, Texas 77204 and Ramanan Krishnamoorti, Chemical Engineering, University of Houston, 4800 Calhoun, Houston, TX 77204 - 4004.

New formulations of non-steroidal anti-inflammatory drugs (NSAIDs) pre associated with zwitterionic phospholipids as safer NSAIDs are emerging. While some understanding on the interactions between NSAIDs and lipids exist, the molecular basis of such interactions is not very clear. Simulations have been shown to be powerful tools to get unprecedented molecular details probing into above mentioned interactions.

In this work, our goal is to understand the type of molecular-level interactions between NSAIDs and lipid membranes over the entire physiological pH range using both experiments and simulations as an effort to engineer liposomes as effective drug delivery vehicles as a means to safer NSAIDs. Calorimetry experiments on two most common NSAIDs viz. Aspirin and Ibuprofen show that these drugs reduce the gel-liquid transition temperature of zwitterionic phospholipid indicating clearly strong interactions between the drug and lipid over the pH range of 2-10. Molecular dynamics simulations with Dipalmytoyl phosphatidyl choline(DPPC) as model zwitterionic lipid show that the type of drug association varies from strongly non-polar to strongly electrostatic interaction as the pH varies. The effect of different head groups (anionic, cationic etc.) on the drug binding will be highlighted in context of presenting a broader picture of the interactions between the class of NSAIDs with lipid membranes. Finally, simulations for long length and time scales using coarse-grain models built on the basis of molecular-level information obtained from all-atomistic simulations will be presented.