(565d) Multiscale Simulation Studies on Mechanisms of Poration for Hydrolytically Degradable Diblock Copolymer Membranes

Ortiz, V., Univ.Pennsylvania
Nielsen, S. O., University of Texas at Dallas
Klein, M. L., University of Pennsylvania
Discher, D. E., University of Pennsylvania

Dissipative particle dynamics computer simulations are proposed to give a molecular understanding to the application of aqueous diblock copolymer systems to drug delivery. The use of a hydrolysable monomer as the hydrophobic block leads to a destabilization of the vesicle membrane due to the increase in the hydrophilic molecular weight fraction (fEO) of the chains, which makes them prefer high curvature conformations such as worm-like and spherical micelles. Experimental work suggests that aggregation of these micelle forming chains provokes a local phase transition to the micellar state, causing poration of the membrane with eventual release of the encapsulated hydrophilic drug and disintegration of the vesicle. In this study, free-energy techniques are employed to examine the microdomain formation by high fEO chains, leading to poration, by using a coordination number reaction coordinate. Additionally, results from atomistic studies on percolation of water into the membrane hydrophobic core will be reported for PLA.