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

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Abstract

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.

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Acknowledgements

TEM was performed at the University of Texas Southwestern Medical Center Molecular and Cellular Imaging Facility. We would like to acknowledge financial support from the American Heart Association Scientist Development Award 073520N and NIH grants HL082644 and HL091232 (K.N.). Official contribution of NIST; not subject to copyright in the United States.

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Correspondence to Thomas Q. Chastek.

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Thuy T. Chastek and Aniket Wadajkar: Both authors contributed equally.

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Table S1

Impact of surfactant and initiator concentration in PNIPAM microgel synthesis. (DOC 47 kb)

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Chastek, T.T., Wadajkar, A., Nguyen, K.T. et al. Polyglycol-templated synthesis of poly(N-isopropyl acrylamide) microgels with improved biocompatibility. Colloid Polym Sci 288, 105–114 (2010). https://doi.org/10.1007/s00396-009-2144-7

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  • DOI: https://doi.org/10.1007/s00396-009-2144-7

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