A Structural and Thermodynamic Study of Doxorubicin in Lipid Membrane Models

Doxorubicin (DOX) is one of the most efficient antitumor drugs in numerous cancer therapies. Its incorporation into lipid-based nanocarriers, such as liposomes, improves the drug targeting into tumor cells and reduces drug side effects. The carriers' lipid composition is expected to affect the interactions of DOX and its partitioning into liposomal membranes. In this context, numerical simulation methods are of great value in designing and determining promising lipid compositions, providing unique information on drug-membrane interactions at the atomic/molecular level of resolution. This speed talk will highlight the capabilities of a theoretical framework developed in our research group combining classical molecular dynamics simulations and free energy calculations to elucidate the molecular mechanism of penetration and partitioning of DOX into potential liposome membrane compositions. Such molecular knowledge, synergically combined with experiments, can help the improvement of the therapeutic efficacy of liposomal anticancer drug products by optimizing their formulations.