Modulating the phase transition temperature and thermosensitivity in N-isopropylacrylamide copolymer gels

Temperature-responsive copolymer (or ternary copolymer) gels of N-isopropylacrylamide (IPAAm) were synthesized with hydrophobic alkyl methacrylate (RMA), hydrophilic acrylamide (AAm), N,N'-dimethylacrylamide (DMAAm), and N-acryloylpyrrolidine (APy) as comonomers. The effects of these comonomers on the phase transition temperature (LCST) and the thermosensitivity have been discussed. The LCST of poly(IPAAm) gel in phosphate buffered saline (PBS) was lowered by the introduction of hydrophobic RMA, and the change in equilibrium swelling ratio with temperature change became smaller with an increase in RMA content. However, a stable skin layer to achieve complete 'on-off' regulation of drug release was formed at a higher temperature by RMA due to hydrophobic interaction of alkyl chains. The LCST of poly(IPAAm-co-AAm) gel increased with an increase in AAm content. However, the thermosensitivity of the gel became smaller. It was suggested that hydrophilic AAm prevented the formation of a dense skin layer at a higher temperature. It was difficult to obtain a complete 'off' state due to an insufficiently dense skin layer in order to stop the drug release. The LCST was raised and great thermosensitivity was possible by the introduction of DMAAm or APy. Poly(IPAAm-co-DMAAm) enabled 'on-off' drug release in response to smaller temperature changes around the body temperature. The molecular design to control transition temperature and thermosensitivity of gel was established.