Abstract Small aromatic molecules are known to interact with poly(N-isopropylacrylamide) (PNIPA) based hydrogels, one of the most frequently employed polymers in temperature induced drug delivery systems. These interactions are poorly understood at the molecular level. In this article we investigate PNIPA both at the macroscopic and at the molecular level using measurements of swelling, differential scanning microcalorimetry (DSC), X-ray powder diffraction (XRD) and solid state 1H NMR methods. The nature and the strength of the interactions affect the efficiency and kinetics of drug delivery. Phenols exert a major influence on PNIPA by reducing its phase transition temperature. The effect depends linearly on the phenol concentration, and is influenced also by the number of phenolic OH groups, as well as their relative positions. The strong interaction between phenol and the polymer that is detected by NMR hinders the crystallisation of phenol when the water is gradually evaporated. The aminoethyl phenol derivative dopamine has a much more limited effect, but in the opposite direction - the transition temperature increases slightly. The strong interaction observed among the dopamine molecules disables the polymer-dopamine interaction and favours crystallization of the dopamine when water is removed. These results reveal that embedding the drugs into polymer matrices for controlled delivery can alter the crystallinity of the stored molecules. As morphology is one of the crucial factors in delivery, this may compromise the rate and the efficiency of release.
Manek, E., Domján, A., Madarász, J., & László, K. (2015). Interactions in aromatic probe molecule loaded poly(N-isopropylacrylamide) hydrogels and implications for drug delivery. European Polymer Journal, 68, 657–664. https://doi.org/10.1016/j.eurpolymj.2015.03.043