Molecular Interactions—Drugs and Lipid Membranes

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Understanding the pharmacokinetic and pharmacodynamic behavior of drugs is critical in their efficient use. The interactions between the drugs and lipid membranes is one of the key elements in the in vivo behavior of such drugs and vital to tailor the pharamacokinetic and phamacodynamic characteristics of the drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs and e.g., Aspirin and Ibuprofen) mainly used for their pain and fever reducing action also cause well known side effect called gastrointestinal (GI) toxicity with chronic usage. NSAID-

Phosphocholine lipid complexes are purported to be safer alternatives wherein NSAIDs are pre-associated with lipid vesicles (figure below) and preliminary laboratory based tests indicate a potential decrease in GI toxicity. However, the interactions between NSAIDs and lipid membranes are not completely elucidated.

The Krishnamoorti group’s focus is to understand the interactions between various NSAIDs and lipid membranes at a molecular level using both experiments and simulations. Macro measure experiments like differential scanning calorimetry clearly indicate that the drugs partition into the bilayer. Using molecular dynamics simulations we are systematically addressing the various aspects like thermodynamics, diffusion, concentration effects etc. of these drugs in lipid membranes.

Some of the results clearly provide deeper insight which is difficult to obtain in experiments. This also helped the group design various neutron scattering experiments in a way that will systematically address and complement our simulations results. Their preliminary round of small angle neutron scattering, neutron reflectivity and neutron spin echo experiments clearly corroborate both macro and molecular level effects of these drugs on lipid vesicles and the membranes.

The group collaborates with Len Lichtenberger & Vasanthi Jayaraman (UTHSC) and Rob Raphael (Rice).

Short Biography
Professor Ramanan Krishnamoorti received his B.Tech from IIT Madras and his Ph.D. from Princeton University, and pursued postdoctoral studies at Caltech and Cornell. In addition to teaching and research, Dr. Krishnamoorti serves as the college’s associate dean for research. He is the recipient of a 1999-2004 NSF CAREER Award, a 2000 Cullen College of Engineering Junior Faculty Research Award, and the 2001 UH Award for Excellence in Research and Scholarship.