Abstract
Cell membranes are often the main and often final barriers for drug delivery. Little is known how hydrophobic drugs such as paclitaxel penetrate through cell membranes. Here we investigate interactions between paclitaxel and a model cellular membrane of palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at the molecular level, using multiscale simulation with all-atomistic1 and coarse-grained models. We simulate several multiple systems of POPC bilayer membrane with several different paclitaxel concentrations in the membrane. Additionally, we calculate the free energy profile across the membrane interface, to compare with previously reported experimental measurements. Furthermore, coarse-grained models of the drug are refined2 to match the all-atomistic free energy profile. Along with the corresponding atomistic simulations, the coarse-grained models provide essential tools to investigate the concentration-dependent behavior of the drug in the membrane. For example, we examine the preferred positioning and orientation of the drug, anisotropic directional diffusion and aggregation over the extended timescale and system size. A better understanding of the interactions between hydrophobic drugs and model membranes and their transport will provide molecular-level insights of the drug delivery process.1.Kang, M.; Loverde, S. M., Molecular Simulation of the Concentration-Dependent Interaction of Hydrophobic Drugs with Moel Cellular Membranes. Journal of Physical Chemistry B 2014, Just Accepted Manuscript.2.Loverde, S. M.; Klein, M. L.; Discher, D. E., Nanoparticle Shape Improves Delivery: Rational Coarse Grain Molecular Dynamics (rCG-MD) of Taxol in Worm-Like PEG-PCL Micelles. Advanced materials 2012, 24 (28), 3823-30.
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