(482g) Molecular Simulations of Liposomal Anti-Cancer Drug Carriers | AIChE

(482g) Molecular Simulations of Liposomal Anti-Cancer Drug Carriers


Boehler, E. - Presenter, North Carolina State University

Liposomes have gained much attention recently due to their ability to mediate the intracellular delivery of cancer therapies. Liposomes are artificial vesicles composed of phospholipid bilayer membranes; they can transport both hydrophilic and hydrophobic drugs. Two major goals of liposomal anti-cancer drug delivery are to promote the accumulation and retention of drug-carrying liposomes in tumor cells and to trigger the release of drug molecules inside the cells. A new intermediate resolution model of liposomal drug carriers is used to determine how the properties of the lipid molecules affect their drug trapping efficiencies and to analyze how drug release kinetics changes in response to different external stimuli. The model is essentially a discontinuous version of the ?Martini? model for lipids; it is designed for use with discontinuous molecular dynamics (DMD) simulation, a very fast alternative to traditional molecular dynamics simulation. The model is applied to aqueous bilayers composed of two types of phospholipids: those containing phosph-L-serine (PS) head groups and those containing phosphatidylcholine (PC) head groups. Liposomes composed of these species have been found experimentally to phase separate into heterogeneous domains (rafts) as the pH is lowered. Runs are conducted to determine how the tail lengths and mole ratios of the PC and PS phospholipids and the presence of targeting functionalities affect: (1) the formation of heterogeneous domains and membrane permeability, (2) the release of model drug molecules through the leaky liposome surface, and (3) fusion of the liposomal membrane to the endosomal membrane. The results are compared to experimental results found in the Sofou lab.