Polyglycol-templated synthesis of poly(N-isopropyl acrylamide) microgels with improved biocompatibility

We report on the synthesis and characterization of thermally responsive poly(N-isopropyl acrylamide) (PNIPAM) nanoparticle hydrogels (i.e., microgels). Microgels with narrow size distributions were synthesized after optimizing the concentrations of monomer, surfactant, and initiator. Polyglycol block copolymers (trade name Pluronic) and sodium dodecylsulfate (SDS) surfactants were compared. In all cases, the particles' size decreased with increasing surfactant concentration, and comparable sizes could be produced with any of the surfactants. The choice of surfactant, however, had a significant influence on the biocompatibility of the PNIPAM microgels. The copolymer-stabilized microgels were less cytotoxic than those stabilized by SDS, as measured using 3(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assays. Even after dialysis (for 3 days) to remove most surfactant, the SDS-based microgels remained more cytotoxic than particles prepared with Pluronics. After exposing cells to polyglycol surfactant solutions, it was found that the polyglycol with highest fraction of polyethylene oxide (Pluronic F127) showed the lowest level of cytotoxicity over the studied range of concentrations. Similarly, PNIPAM microgels synthesized with this surfactant had the lowest level of cytotoxicity. Finally, drug loading and release studies were performed using doxorubicin as a model drug.