Influence of Solvent on the Drug-Loading Process of Amphiphilic Nanogel Star Polymers

We present an all-atom molecular dynamics study of the effect of a range of organic solvents (dichloromethane, diethyl ether, toluene, methanol, dimethyl sulfoxide, and tetrahydrofuran) on the conformations of a nanogel star polymeric nanoparticle with solvophobic and solvophilic structural elements. These nanoparticles are of particular interest for drug delivery applications. As drug loading generally takes place in an organic solvent, this work serves to provide insight into the factors controlling the early steps of that process. Our work suggests that nanoparticle conformational structure is highly sensitive to the choice of solvent, providing avenues for further study as well as predictions for both computational and experimental explorations of the drug-loading process. Our findings suggest that when used in the drug-loading process, dichloromethane, tetrahydrofuran, and toluene allow for a more extensive and increased drug-loading into the interior of nanogel star polymers of the composition studied here. In contrast, methanol is more likely to support shallow or surface loading and, consequently, faster drug release rates. Finally, diethyl ether should not work in a formulation process since none of the regions of the nanogel star polymer appear to be sufficiently solvated by it.