Phenol release from pNIPAM hydrogels: scaling molecular dynamics simulations with dynamical density functional theory

We employed molecular dynamic simulations (MD) and the Bennett's acceptance ratio method to compute the free energy of transfer, Δ G trans , of phenol, methane, and 5-fluorouracil (5-FU), between bulk water and water-pNIPAM mixtures of different polymer volume fractions, p . For this purpose, we first calculate the solvation free energies in both media to obtain Δ G trans . Phenol and 5-FU (a medication used to treat cancer) attach to the pNIPAM surface so that they show negative values of G trans irrespective of temperature (above or below the lower critical solution temperature of pNIPAM, T c ). Conversely, methane switches the Δ G trans sign when considering temperatures below (positive) and above (negative) T c . In all cases, and contrasting with some theoretical predictions, Δ G trans maintains a linear behavior with the pNIPAM concentration up to large polymer densities. We have also employed MD to compute the diffusion coefficient, D , of phenol in water-pNIPAM mixtures as a function of p in the diluted limit. Both Δ G trans and D as a function of p are required inputs to obtain the release halftime of hollow pNIPAM microgels through Dynamic Density Functional Theory (DDFT). Our scaling strategy captures the experimental value of 2200 s for 50 μm radius microgels with no cavity, for p 0.83 at 315 K. We obtain the microgel extent of release by feeding free energies and diffusion coefficients from MD to DDFT. We found a good agreement with the available experimental data for pNIPAM particles loaded with phenol.