(416e) Uncovering the Effect of Lipid Headgroups on the Mechanical Properties of Ultra-Deformable Liposome Membranes Using Molecular Dynamics Simulations

The challenge of enhancing drug delivery efficacy to tumor sites remains a central topic in the field of cancer research. Lipid nanoparticles (LNPs) are widely recognized as promising drug delivery vehicles due to their numerous advantages, including stability, bioavailability, flexibility, and low toxicity. However, the dense tissues and fibroblasts surrounding certain types of tissues such as triple negative breast cancer (TNBC) regions necessitate the use of more fluidic LNPs that can squeeze through fibrous regions for improved drug delivery efficacy. In order to identify formulations of more deformable LNPs, classical molecular dynamics (MD) simulations were employed to investigate the impact of adding 5 lipids with different headgroups but the same lipid tails, to DOPC lipid bilayers on their mechanical properties. As expected, the analyses of order parameters and terminal methyl group distribution demonstrate that there is minimal variation observed among the different headgroups, given that all lipids have the same tail structure. However, our results indicate that a decrease in the area compressibility modulus, which corresponds to a softer lipid bilayer, could be caused by a more negative self-interaction energy between DOPC and the secondary lipids, and by a more closely clustered distribution of secondary lipids.