PH- and temperature-responsive hydrogels of acrylic acid, N-isopropylacrylamide and a non-ionic surfmer: phase behaviour, swelling properties and drug release

Abstract

Copolymer hydrogels composed of N-isopropylacrylamide (NIPAM), acrylic acid (AA) and the non-ionic surfactant monomer (surfmer) ω-methoxy poly(ethylene oxide)40undecyl-α-methacrylate (PEO-R-MA-40) were prepared and studied with regard to swelling behaviour and drug release behaviour. The gels were prepared upon γ-irradiation of the corresponding aqueous comonomer solution in a one-step reaction. Transparent, stable hydrogels were obtained. Studies of light transmission indicate a dual pH- and T-responsive behaviour, which originates from the AA and NIPAM content of the gels, respectively. Presence of large amounts of surfmer increases the phase transition temperature, but also increases the network density, which lowers the permeability of the gels. Swelling properties and release of ibuprofen (Ibu) were studied in simulated gastric fluid (SGF, pH 1) and phosphate buffer solution (PBS, pH 6.8). It was found that swelling and release are controlled by the nature and quantity of comonomers, pH, temperature and ionic strength of the aqueous phase. Swollen gels shrink in SGF and PBS, whereas dry gels exhibit a strong swelling both in SGF and PBS. Copolymer gels of AA and surfmer exhibit a strong, linear release of Ibu in SGF and PBS. If NIPAM is copolymerized in the gel, the drug release is decelerated in SGF probably due to formation of hydrogen bonds between NIPAM and Ibu at low pH. For example, a gel composed of 10 % (w/w) NIPAM, 1 % (w/w) AA and 1.5 % (w/w) surfmer exhibits a release of 10 % within 2 h in SGF and 58 % within 20 h in PBS.