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Improving the Biocompatibility of Thermo-Sensitive Poly(N-Isopropyl Acrylamide) Nanoparticles for Drug Delivery



Thuy Chastek, Aniket Wadajkar, Kytai T. Nguyen, Steven Hudson, Thomas Q. Chastek


We report on the synthesis of monodisperse thermally responsive poly(N-isopropylacrylamide) (PNIPAM) nanoparticle hydrogels (i.e., microgels). PNIPAM microgels were synthesized using Pluronic surfactants (L64, P65, P85, and F127) to increase their biocompatibility. Microgels with narrow size distributions were synthesized after optimizing the concentrations of monomer, the surfactant, and initiator. It was found that the choice of surfactant did not greatly affect the resulting microgel size. In all cases, however, the particles size decreased with increasing surfactant concentration. The choice of surfactant was found to impact the biocompatibility of the PNIPAM nanoparticles. In all cases, the Pluronic-stabilized microgels were less cytotoxic than those stabilized by sodium dodecylsulfate (SDS), as measured using 3(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays. In fact, even though removal of SDS through 3 days of dialysis decreased the particles cytotoxicity, they remained more cytotoxic than undialyzed particles prepared with Pluronics. When comparing the Pluronics themselves, it was found that F127, which has the highest fraction of polyethylene oxide, showed the lowest level of cytotoxicity over the studied range of concentrations. Similarly, PNIPAM microgels synthesized using Pluronic F127 had the lowest level of cytotoxicity. Finally, drug loading and release studies were performed using doxorubicin as a model drug. PNIPAM nanoparticles synthesized using Pluronic surfactants showed a higher amount of doxorubicin release than PNIPAM nanoparticles synthesized using SDS at 37 C over the same period of time.


N-isopropylacrylamide, cytotoxicity, temperature-sensitive nanoparticles, pluronic, fibroblasts, drug delivery


Chastek, T. , Wadajkar, A. , Nguyen, K. , Hudson, S. and Chastek, T. (2009), Improving the Biocompatibility of Thermo-Sensitive Poly(N-Isopropyl Acrylamide) Nanoparticles for Drug Delivery, Biomaterials, [online], (Accessed July 22, 2024)


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Created November 17, 2009, Updated October 12, 2021