(773c) Serum Albumin Interactions with Doxorubicin-Loaded Graphene Oxide in an Aqueous Environment with Blood pH Level: A Molecular Dynamics Simulation Study

Graphene oxide (GO) as a nanocarrier has been shown to possess desirable delivery and targeting properties for doxorubicin (DOX) anticancer drug [1]. In general, an effective drug delivery system should be able to load the drug, carry it in the blood stream, and release it at the action site. In this study, we use molecular dynamics (MD) simulation to investigate the interactions between albumin, which has a crucial role in the pharmacokinetics and pharmacodynamics of nanoparticulate drug delivery systems, and DOX-loaded GO in an aqueous environment mimicking blood with a pH level of 7.4. Our objective is to elucidate the effect of serum albumin on the stability of the drug delivery system during intravenous delivery. Understanding these fundamental molecular-level interactions will help in designing improved nanocarriers for an efficient delivery of DOX to the action site without any appreciable premature release of the drug in the blood stream. We are performing a series of MD simulations of the DOX/GO/albumin system in the NAMD software using the CHARMM force field at the blood pH level and body temperature using an implicit solvent method. DOX-albumin, albumin-GO, and DOX-GO interactions are calculated and compared. Preliminary results will be given and a direction for future work will be outlined.

[1] M. Mahdavi, F. Rahmani, S. Nouranian, Molecular simulation of pH-dependent diffusion, loading, and release of doxorubicin in graphene and graphene oxide drug delivery systems, Journal of Materials Chemistry B 4(46) (2016) 7441-7451.