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.
References
Kim IS, Jeong YI, Cho CS, Kim SH (2000) Int J Pharm 205:165–172
Ramanan RMK, Chellamuthu P, Tang LP, Nguyen KT (2006) Biotechnol Progr 22:118–125
Tasdelen B, Kayaman-Apohan N, Guven O, Baysal BM (2004) Polym Adv Technol 15:528–532
Lopez VC, Raghavan SL, Snowden MJ (2004) React Funct Polym 58:175–185
Chen HY, Gu YQ, Hu YZ (2008) J Mater Sci - Mater Med 19:651–658
Barratt G (2003) Cell Mol Life Sci 60:21–37
Rzaev ZMO, Dincer S, Piskin E (2007) Prog Polym Sci 32:534–595
Lyon LA, Meng ZY, Singh N, Sorrell CD, John AS (2009) Chem Soc Rev 38:865–874
Zha L, Hu J, Wang C, Fu S, Elaissari A, Zhang Y (2002) Colloid Polym Sci 280:1–6
Kratz K, Hellweg T, Eimer W (2000) Colloids Surf A 170:137–149
Hoare T, Pelton R (2004) Macromolecules 37:2544–2550
Gao J, Frisken BJ (2005) Langmuir 21:545–551
Chen HY, Zhang J, Qian ZY, Liu F, Chen XY, Hu YZ, Gu YQ (2008) Nanotechnology 19:185707
Taillefer J, Jones MC, Brasseur N, Van Lier JE, Leroux JC (2000) J Pharm Sci 89:52–62
Hsiue GH, Chang RW, Wang CH, Lee SH (2003) Biomaterials 24:2423–2430
Leobandung W, Ichikawa H, Fukumori Y, Peppas NA (2002) J Control Release 80:357–363
Rahimi M, Kilaru S, Sleiman GEH, Saleh A, Rudkevich D, Nguyen KT (2008) J Biomed Nanotech 4:482–490
Pelton RH, Chibante P (1986) Colloids Surf 20:247–256
Wu X, Pelton RH, Hamielec AE, Woods DR, McPhee W (1994) Colloid Polym Sci 272:467–477
McPhee W, Tam KC, Pelton R (1993) J Colloid Interface Sci 156:24–30
Pelton R (2004) Macromol Symp 207:57–65
Gao J, Frisken BJ (2003) Langmuir 19:5217–5222
Andersson M, Maunu SL (2006) J Polym Sci, Part B: Polym Phys 44:3305–3314
Tan BH, Tam KC (2008) Adv Colloid Interface Sci 136:25–44
Pelton R (2000) Adv Colloid Interface Sci 85:1–33
Keerl M, Pedersen JS, Richtering W (2009) J Am Chem Soc 131:3093–3097
Cserhati T, Forgacs E, Oros G (2002) Environ Int 28:337–348
Hrabák A, Antoni F, Szabó MT (1982) Bull Environ Contam Toxicol 28:504–511
Konak C, Panek J, Hruby M (2007) Colloid Polym Sci 285:1433–1439
Alexandridis P, Hatton TA (1995) Colloids Surf A 96:1–46
Nagarajan R (1999) Colloids Surf B: Biointerfaces 16:55–72
Kabanov AV, Batrakova EV, Alakhov VY (2002) Adv Drug Deliv Rev 54:759–779
Kabanov AV, Batrakova EV, Alakhov VY (2002) J Control Release 82:189–212
Allen C, Maysinger D, Eisenberg A (1999) Colloids Surf B: Biointerfaces 16:3–27
Venne A, Li S, Mandeville R, Kabanov A, Alakhov V (1996) Cancer Res 56:3626–3629
Oh KT, Bronich TK, Kabanov AV (2004) J Control Release 94:411–422
Vandervoort J, Ludwig A (2002) Int J Pharm 238:77–92
Hoare T, Pelton R (2006) J Colloid Interface Sci 303:109–116
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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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