(107e) Developing Optimal Hyper-Elastic Liposomes for Drug Delivery: Insights from Molecular Simulations

Liposomes and lipid nanoparticles are commonly used in delivery of drugs that have low stability or high cytotoxicity. While the effects of properties such as liposome size, shape and surface charge on drug delivery applications have been widely studied, liposome elasticity remains significantly underexplored. Results from a recent study [1] indicate that hyper-elastic liposomes made of DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), where their stiffness was modulated by fillers inside the liposomes, had increased uptake by human breast cancer cells in vitro, and had significantly larger tumor accumulation in vivo compared to more rigid liposomes. These results suggest that hyper-elastic liposomes might be promising drug delivery vehicles, especially for diseases characterized by dense fibrous tissues (certain types of cancer, pulmonary or liver fibrosis), where we hypothesize more fluidic liposomes could squeeze into the fibrotic regions and efficiently deliver their cargo. In this talk, I will provide an overview of our molecular simulation studies, which aimed at fundamentally understanding how the mechanical properties of the liposomes are affected by variables such as the molecular structure of the lipids (tails, headgroups), the composition of the liposome, and the presence of embedded hydrophobic drugs.

[1] P. Guo, D. Liu, K. Subramanyam, B. Wang, J. Yang, J. Huang, D. T. Auguste and M. A. Moses, “Nanoparticle elasticity directs tumor uptake”, Nature Communications 2018, 9, 130.