Modeling the impact of drug-nanocarriers in lipid membranes

A coarse-grained framework for molecular dynamics (CG-MD) simulations based on the MARTINI force field was developed to tackle interactions between ionic G5 dendrimers and nonionic Pluronic micelles with diverse amphiphilic characters as drug-loaded nanocarriers in contact with two biological membranes, the anionic 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) + 1-palmitoyl-2-oleoyl-glycero-3-phosphatidylglycerol (POPG) and the neutral dipalmitoyl phosphatidylcholine. Simulations showed that drug-nanocarrier stability relies on a delicate balance of their amphiphilic character and Coulombic interactions. Pluronic micelles yielded lower undesired drug leaks into the water phase compared with the cationic G5 dendrimers, which either remained attached to Pluronic moieties or remained between them and the membrane surface. An interesting feature of Pluronic micelles was their tendency to be disrupted and absorbed into the membranes. Hydrophilic micelles showed improved drug stability, avoiding early release of doxorubicin and gemcitabine drugs. When the Pluronic micelles are disrupted and absorbed into the charged membrane, the hydrophilic pluronic segments were depleted toward the membrane surface, retaining the drugs within. Overall, the CG-MD framework yields a detailed molecule-scale picture of the cooperative Coulombic and amphiphilic effects between charged moieties in contact with membrane surfaces.