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

Abstract

We employed molecular dynamic simulations (MD) and the Bennett's acceptance ratio method to compute the free energy of transfer, ΔG_trans, of phenol, methane, and 5-fluorouracil (5-FU), between bulk water and water–pNIPAM mixtures of different polymer volume fractions, ϕ_p. For this purpose, we first calculate the solvation free energies in both media to obtain ΔG_trans. Phenol and 5-FU (a medication used to treat cancer) attach to the pNIPAM surface so that they show negative values of ΔG_trans irrespective of temperature (above or below the lower critical solution temperature of pNIPAM, T_c). Conversely, methane switches the ΔG_trans sign when considering temperatures below (positive) and above (negative) T_c. In all cases, and contrasting with some theoretical predictions, ΔG_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 ϕ_p in the diluted limit. Both ΔG_trans and D as a function of ϕ_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 ϕ_p ≃ 0.83 at 315 K.