Veyis KARAKOÇ, Deniz TÜRKMEN, Huma SHAİKH, Nilay BERELİ, Cenk A. ANDAC, Adil DENİZLİ

Poli N-izopropilakrilamid bazlı kriyojelin sentez ve karakterizasyonu

B u çalışmanın amacı NIPA’nın düşük kritik çözelti sıcaklığı LCST civarındaki sıcaklık değişimlerine karşı pH’ya ve sıcaklığa duyarlı poli N-izopropilakrilamid-N metakriloil- L -histidin [poli NIPA-MAH ] monolitik kriyojelin nanoyapısındaki değişimleri açıklamaktır. Poli NIPA-MAH kriyojel plastik şırınga içerisinde NIPA’nın fonksiyonel komonomer olarak kullanılan MAH ile serbest radikal kriyokopolimerizasyonu ile hazırlanmış olup N,N-metilen-bisakrilamid MBAAm çapraz bağlayıcı olarak kullanıldı. Kriyopolimerizasyon N,N,N,Ntetrametilen diamin TEMED ve amonyum persülfat APS çifti ile buz banyosunda sıfırın altındaki sıcaklıkta -16ºC başlatıldı. Poli NIPA-MAH kriyojelin LCST değeri 34ºC olarak bulundu. Poli NIPA-MAH kriyojelin yüzey morfolojisi ve yığın yapısı taramalı elektron mikroskobu SEM ile belirlenmiştir. 60–100 µm por çapına sahip poli NIPA-MAH kriyojel 42.6 m2/g polimer değerinde yüzey alanına sahiptir. Poli NIPA-MAH kriyojel Fourier dönüşümlü kızılötesi spektrometre FTIR ve şişme testi ile karakterize edildi. Kuru kriyojelin denge şişme derecesi 22.08 g HO/g olarak bulundu. Geleneksel jellerle karşılaştrıldığında, bu gözenekli kriyojel şekli NIPA’ya hızlı yanıt verme olanağı sağlar

Anahtar Kelimeler:

N-izopropilakrilamid NIPA, sıcaklığa duyarlı polimerler, kriyojeller, histidin

Synthesis and Characterization of Poly N- isopropylacrylamide Thermosensitive Based Cryogel

The aim of this study was to reveal the changes in the nanostructure of the thermo-sensitive poly N- isopropylacrylamide-N methacryloyl- L -histidine [poly NIPA-MAH ] monolithic cryogel with changing temperature around lower critical solution temperature LCST of NIPA. Poly NIPA-MAH cryogel was prepared by free radical cryopolymerization of NIPA with MAH as a functional comonomer and N,N-methylene- bisacrylamide MBAAm as crosslinker directly in a plastic syringe. Cryo-polymerization was initiated by N,N,N,N-tetramethylene diamine TEMED and ammonium persulfate APS pair at subzero temperature -16ºC in an ice bath. LCST of poly NIPA-MAH cryogel was found to be 34ºC. The surface morphology and bulk structure of poly NIPA-MAH cryogel was revealed with scanning electron microscopy SEM . Poly NIPA- MAH cryogel with 60–100 μm pore diameter has a specific surface area of 42.6 m2/g polymer. Poly NIPA- MAH cryogel was characterized by Fourier transform infrared spectrometer FTIR and swelling test. The equilibrium swelling degree of poly NIPA-MAH cryogel was 22.08 g H2O/g for dry cryogel. The presence of NIPA makes cryogel morpholgy highly porous and differentiates it from conventional gels.

Keywords:

N-isopropylacrylamide NIPA, thermosensitive polymers, cryogels, histidine,

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1. A. Kumara, A. Srivastava, I. Y. Galaev, B. Mattiasson, Smart polymers: Physical forms and bioengineering applications, Prog. Polym. Sci., 32 (2007) 1205.
2. E. S. Gil, S. M. Hudson, Stimuli-reponsive polymers and their bioconjugates, Prog. Polym. Sci., 29 (2004) 1173.
3. J. Zhang, R.D.K. Misra, Magnetic drug-targeting carrier encapsulated with thermosensitive smart polymer: Core–shell nanoparticle carrier and drug release response, Acta Biomaterialia, 3 (2007) 838.
4. H. Ichikawa, Y. Fukumori, A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(Nisopropylacrylamide) gel dispersed in ethylcellulose matrix, J. Cont. Rel., 63 (2000) 107.
5. A. Kondo, H. Fukuda, Preparation of thermo-sensitive magnetic hydrogel microspheres and application to enzyme immobilization, J. Ferment. Bioeng., 84 (1997)337.
6. A. Kumar, M. Kamihira, I. Yu. Galaev, S. Iijima, and B. Mattiasson; Binding of Cu(II)-Poly(Nisopropylacrylamide/ vinylimidazole) Copolymer to Histidine-Tagged Protein: A Surface Plasmon Resonance Study, Langmuir, 19 (2003) 865.
7. E. Kalaycıoğlu, S. Patır, E. Pişkin, Poly(N-isopropylacryl amide-co-2-methacryloamido histidine) copolymers and their interactions with human immunoglobulin-G, Langmuir, 19 (2003) 9538.
8. H. Tokuyama, T. Iwama, Temperature-swing solidphase extraction of heavy metals on a poly(Nisopropylacrylamide) hydrogel, Langmuir, 23 (2007) 13104.
9. R. Pelton, Temperature-sensitive aqueous microgels, Adv. Coll. Int. Sci., 85 (2000) 1.
10. M. Turk, S. Dincer, E. Piskin, Smart and cationic poly(NIPA)/PEI block copolymers as non-viral vectors: in vitro and in vivo transfection studies, J. Tissue Eng. Regen. Med., 1 (2007) 377.
11. N. Shamim, H. Liang, K. Hidajat, M.S. Uddin, Adsorption, desorption, and conformational changes of lysozyme from thermosensitive nanomagnetic particles, J. Coll. Int. Sci., 320 (2008) 15.
12. M. Türk, Z. M. O. Rzayev, S. A. Khalilova, Bioengineering functional copolymers, XIV. Synthesis and interaction of poly(N-isopropylacryl amide-co-3,4-dihydro-2Hpyran-alt-maleic anhydride)s with SCLC cancer cells, Bioorganic & Medicinal Chemistry 18 (2010) 7975.
13. K. Nagase, J. Kobayashi, T. Okano, Temperatureresponsive intelligent interfaces for biomolecular separation and cell sheet engineering, J. R. Soc. Interface, 6 (2009) 293.
14. N. Bereli, M. Andac, G. Baydemir, R. Say, I. Y. Galaev, A. Denizli, Protein recognition via ion-coordinated molecularly imprinted supermacroporous cryogels, J. Chrom. A, 1190 (2008) 18.
15. V. I. Lozinsky, I. Y. Galaev, F. M. Plieva, I. N. Savin, H. Jungvid, B. Mattiasson, Polymeric cryogels as promising materials of biotechnological interest, Trends in Biotech., 21 (2003) 445.
16. W. Xue, S. Champ , M. B. Huglina, T. G. J Jones, Rapid swelling and deswelling in cryogels of crosslinked poly(N-isopropylacrylamide-co-acrylic), Eu. Pol. J. 40 (2004) 703.
17. J. Kobayashi, A. Kikuchi, K. Sakai, T. Okano, Aqueous chromatography utilizing pH-/temperature-responsive polymer stationary phases to separate ionic bioactive compounds, Anal. Chem., 73 (2001) 2027.
18. H. Kanazawa, M. Nishikawa, A. Mizutani, C. Sakamoto, Y. M.-Murase, Y. Nagata, A. Kikuchi, T. Okano, Aqueous chromatographic system for separation of biomolecules using thermoresponsive polymer modified stationary phase, J. Chrom. A., 1191(2008) 157.
19. P. Maharjan, B. W. Woonton, L. E. Bennett, G. W. Smithers, K. De Silva, M. T. W. Hearn, Novel chromatographic separation–The potential of smart polymers, Innov. Food Sci. Emerg. Tech.,9 (2008)232.
20. W. Zhang, L. Qin, X.-W. He, W.-Y. Li, Y.-K. Zhang, Novel surface modified molecularly imprinted polymer using acryloyl-B-cyclodextrin and acrylamide as monomers for selective recognition of lysozyme in aqueous solution, J. Chrom. A, 1216 (2009) 4560.
21. H. L. Liu, M. Z. Liu, L. W. Ma, J. Chen, Thermoand pH-sensitive comb-type grafted poly(N,Ndiethylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors, Eu. Polym. J., 45 (2009) 2060.
22. Y. Liu , X. Cao, M. Luo, Z. Le, W. Xu, Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release, J. Coll. Int. Sci., 329 (2009) 244.
23. E.J. Kim, S. Cho, S. H. Yuk, Polymeric microspheres composed of pH/temperature polymer complex, Biomat., 22 (2001) 2495
24. G. Fundueanu, M. Constantin, P. Ascenzi, Preparation and characterization of pH- and temperaturesensitive pullulan microspheres for controlled release of drugs, Biomat., 29 (2008) 2767.
25. J. M. Benns, J.-S. Choi, R. I. Mahato, J.-S. Park, S. W. Kim, pH-Sensitive Cationic Polymer Gene Delivery Vehicle: N -Ac-poly(L - histidine) - graft - poly(Llysine) Comb. Shaped Polymer, Bioconjugate Chem., 11 (2000) 637.
26. H. Yavuz, V. Karakoc, D. Turkmen, R. Say, A. Denizli, Synthesis of cholesterol imprinted polymeric particles, Intern. J. Biol. Macromol., 41 (2007) 8.
27. Y. Çanak, S. Ozkara, S. Akgol, A. Denizli, Pseudo-specific bioaffinity chromatography of immunoglobulin-G, React. & Funct.l Polym., 61 (2004) 369.
28. I. W. Hamley, V. Castelletto, N. M. P. S Ricardo, M. E. N. Pinho, C. Booth, D. Attwood, Z. Yang, A SAXS study of the structure of gels formed by mixtures of polyoxyalkylene triblock copolymers, Polym. Int. 56(2007)88.
29. M. H. Zareie, S. Dincer, E. Piskin, Observation of phase transition of thermo-responsive poly(NIPA)–PEI block copolymers by STM, J. Coll. Int. Sci., 251 (2002) 424.
30. M. Chalal, F. Ehrburger-Dolle, I. Morfin, J.-C. Vial, M.-R. A. de Armas, J. S. Roman, N. Bolgen, E. Piskin, O. Ziane, R. Casalegno, Imaging the structure of macroporous hydrogels by two-photon fluorescence microscopy, Macromol., 42 (2009) 2749.
31. P. Perez, F. Plieva, A. Gallardo, J. S. Roman, M. R. Aguilar, I. Morfin, F. Ehrburger-Dolle, F. Bley, S. Mikhalovsky, I.Y. Galaev, B. Mattiasson, Bioresorbable and nonresorbable macroporous thermosensitive hydrogels prepared by cryopolymerization, role of the cross-linking agent, Biomacromol., 9(2008) 66.
32. H. M. Zareie, E. V. Bulmus, A. P. Gunning, A. S. Hoffman, E. Piskin, V. J. Morris, Investigation of stimuliresponsive copolymer by atomic force microscopy, Polymer, 41(2000)6723.
33. B. Garipcan, A. Denizli, A novel affinity support material for the separation of immunoglobulin G from human plasma, Macromol. Biosci. 2 (2002) 135.
34. N. Bereli, G. Ertürk, M.A. Tümer, R. Say, A. Denizli, Oriented immobilized anti-hIgG via Fc fragmentimprinted PHEMA cryogel for IgG purification, Biomed. Chromatogr., 27 (2013) 599.
35. S. Utku, E. Yılmaz, D. Türkmen, L. Uzun, B. Garipcan, R. Say, A. Denizli, Ion-imprinted thermosensitive polymers for Fe3+ removal from human plasma, Hacettepe J. Biol. & Chem., 36 (2008) 291
36. M. Andaç, I.Y. Galaev, A. Denizli, Dye attached poly(hydroxyethyl methacrylate) cryogel for albumin depletion from human serum, J. Sep. Sci., 35 (2012) 1173.
37. E. Özgür, N. Bereli, D. Türkmen, S. Ünal, A. Denizli, PHEMA cryogel for in-vitro removal of anti-dsDNA antibodies from SLE plasma, Mater. Sci. Eng. C., 31 (2011) 915.
38. S. Aslıyüce, N. Bereli, L. Uzun, M.A. Onur, R. Say, A. Denizli, Ion-imprinted supermacroporous cryogel, for in vitro removal of iron out of human plasma with beta thalassemia. Sep. Purif. Technol., 73 (2010) 243.
39. D. Çimen, A. Denizli, Immobilized metal affinity monolithic cryogels for cytochrome c purification, Colloids Surf. B., 93 (2012) 29.