Nanoparticle Loading in Swollen Polymer Gels: An Unexpected Thermodynamic Twist

Tailoring polymer gel functionality by loading small molecules and nanoparticles is critical for drug delivery and tissue regeneration. Typically, solute loading in gels correlates with the degree of solvent swelling, which is controlled by the crosslink density and polymer/solvent interactions. However, the general assumption that the degree of swelling is the primary factor for nanoparticle loading is incorrect. Here, we demonstrate that the pairwise interactions between polymer, solvent, and solute dictate the solute loading in gels. We performed gel loading studies of ligand-stabilized gold nanoparticles using different solvents, polymer network hydrophobicity, and crosslink densities, and found that nanoparticle distribution between polymer and solvent correlate with calculated thermodynamic partition coefficients. Despite previous assumptions that the maximum nanoparticle loading occurs at the highest degree of gel swelling, we reveal that nanoparticles preferentially load into gels with lower solvent swelling if ligand/polymer interactions are more favorable than ligand/solvent interactions.