(574a) A Mulitscale Simulation Approach to Issues in Drug Delivery

Enhanced drug delivery devices offer a number of benefits, including: increased patient compliance, more even dosages, extended patent-life and marketplace differentiation. We report on a series of multiscale simulations of drug delivery from various depot devices. Multiscale simulation involves techniques ranging from atomistically detailed molecular mechanics models, to coarse-grained representations using dissipative particle dynamics and hybrid methods. At the coarse-grained level some detail is sacrificed in the interest of probing longer length- and time-scales. The utility and benefits of the various methods are discussed. In particular we look at release profiles of drugs from polymeric devices as a function of the relative hydrophobicity of the active ingredient and of the nature of the polymeric device. The role of electrostatic interactions is investigated. In addition we carefully consider issues of coarse-graining and reverse-mapping (replacing a coarse-grained model with its fully atomistic equivalent).