Temperature- and pH-responsive poly(N-isopropylacrylamide-co-methacrylic acid) microgels as a carrier for controlled protein adsorption and release

Herein, we report controlled protein adsorption and delivery of thermo- and pH-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-co-MAA) microgels at different temperatures, pH values and ionic strengths by employing bovine serum albumin (BSA) as a model protein. For these dual-responsive microgels, we found that the BSA adsorption was driven by several of six competing contributions, viz., physical diffusion (PD), hydrophobic interactions (HI), electrostatic attraction (EA), hydrogen bonding (HB) and temperature or pH-induced seizing action (SA_T or SA_pH), depending on the temperature and pH of the solution. Compared to the pure PNIPAM microgels, the higher swelling degree of the PNIPAM-co-MAA microgels allowed a large amount of BSA loading under any experimental conditions. A largest BSA adsorption of 45.1 μg mg^-1 was achieved at 40 °C and pH 4 due to the presence of all six contributions. The BSA adsorption and delivery could be further tuned by changing the crosslinking density within the microgels. The BSA binding onto the microgels was found to be ionic strength dependent, which could be attributed to the charge shielding of Na⁺ ions, salting out of BSA and aggregate formation of the microgels. The adsorbed BSA could be controllably released by adjusting the temperature and pH of the experiment, and with the help of sodium dodecyl sulphate (SDS) addition so as to eliminate each interaction between BSA and the microgels. Thus, this study can be useful to design a stimuli-responsive microgel-based carrier for controlled release of proteins.