Veyis KARAKOÇ, Hamdi ÇELİK, Adil DENİZLİ, Handan YAVUZ, Lokman UZUN

Microporous poly(hydroxyethyl methacrylate) based affinity membranes carrying heparin for cholesterol apheresis

In this study, the preparation of polymeric membranes using bioaffinity technology for application in blood filtration devices is described. Low molecular weight heparin (LMWH) attached poly(hydroxyethyl methacrylate) (PHEMA) based microporous affinity membranes were used for selective removal of cholesterol from hypercholesterolemic human plasma in-vitro. In order to further increase blood-compatibility of affinity membranes, aminoacid based comonomer N-methacryloyl-L-alanine (MAAL) was included in the polymerization recipe. PHEMAAL membranes were produced by a photopolymerization technique and then characterized by swelling test and scanning electron microscope (SEM) studies. In vitro blood-compatibility tests were assessed using modified activated partial thromboplastin time (APTT), prothrombin time (PT) and coagulation time (CT). The water swelling ratio of PHEMAAL increased significantly (133.2%) compared with PHEMA (58%). PHEMAAL membranes have large pores around in the range of 5-10 μm. All the clotting times increased when compared with PHEMA membranes. Loss of platelets and leukocytes was very low. LMWH loading amount was in the range of 87.5-147.2 mg/g. There was a very low non-specific cholesterol adsorption onto the PHEMA membranes, about 0.69 mg/g. LMWH attached PHEMAAL membranes adsorbed cholesterol in the range of 12.7-22.6 mg/g from hypercholesterolemic human plasma.

PDF

___

1. M. Blaha, Acta Med., 46 (2003) 3.
2. H. Mabuchi, Atherosclerosis, 61 (1986) 1.
3. H. Mabuchi, J. Japan Atherosclerosis Soc. 16 (1988) 299.
4. J.L. Goldstein and K.S.E. Dank, Proc. Natl. Acad. Sci., 72 (1975) 1092.
5. N. Koga and Y. Iwata, Atherosclerosis, 90 (1991) 168.
6. M. Eriksson, B. Lantz, L. Berlund, B. Angelin, Acta Med Scand, 221 (1987) 317.
7. G.R. Thompson, Lancet, 1 (1987)1246.
8. W. Wang, H. Xie, L. Sun, L. Qu, L. Wang, Y. Yu, D. Kong, Bimed. Mater., 4 (2009) 1.
9. Y. Homma, Y. Mikami, H. Tamachi, Arteriosclerosis, 5 (1986) 613.
10. G.R. Thompson, Atherosclerosis, 167 (2003) 1.
11. P.J. Lupien, S. Moorjani, M. Lou, D. Brun, C. Gagne, Pediat. Res., 14 (1980) 113.
12. W. Toffel and T. Demant, Proc. Natl. Acad. Sci., 78 (1981) 611.
13. H. Borberg, W. Stoffel, K. Oett, Plasma Ther. Transfus. Technol., 4 (1983) 459.
14. E. Behm, T. Kuroda, N. Yamawaki, Biomat. Artif. Cells Artif. Organs, 15 (1987) 101.
15. K. Thies, S.A. Prigent, C.C. Heuck, Artif. Organs, 12 (1988) 320.
16. Y.M. Lopukhin, V.Y. Zuevsky, S.S. Markin, E.S. Nalivaiko, A.N. Rabovsky, Biomat. Artif. Cells and Artificial Organs,18 (1990) 571.
17. S.N. Pokrovsky, I.Y. Adamova, G.F. Benelovenskaya, Biomat. Artif. Cells and Artif. Organs, 18 (1990) 623-628.
18. A. Denizli and E. Pişkin, J. Chromatogr. B, 670 (1995) 157.
19. F.M. Plieva, B. Mattiasson, Ind. Eng. Chem. Res.,47(12) (2008) 4131.
20. M. Nachman, J. Chromatogr., 597 (1992) 167.
21. C. Charcosset, J. Chem. Technol. Biotechnol., 71 (1998) 95.
22. J.B. Park, 1984, Biomaterials Science and Engineering, Plenum Press. New York (1984).
23. B. Garipcan, N. Bereli, S. Patır, Y. Arıca, A. Denizli, Macromol. Biosci., 1 (2001) 332.
24. A.K. Bajpai, D.D. Misra, J. Appl. Polym. Sci., 102 (2006) 1341.
25. A. Denizli, J. Chromatogr. B, 772 (2002) 357.
26. H.S. Van Damme and J. Feijen in Modern Aspects of Protein Adsorption on Biomaterials, Y.F. Missirlis and W. Lemm eds., Kluwer Academic Publishers, The Netherlands, 1991.
27. A. Tabak, N. Lotan, S. Sideman, A. Tzipiniuk, B. Bleiberg and G. Brook, Life Support Systems, 4 (1986) 355.
28. R.E. Ostlund, Artif. Organs, 11 (1987) 366.
29. G. Smolik, B. Schmidt, U. Baurmeister, H.J. Gurland, Artif. Organs, 13 (1988) 368.
30. B. Schmidt, Ex-vivo evaluation of biocompatibility, Presentation at the Xth Int. Symp. on Hemoperfusion and Immobilized Reactants, Rome, Sept 24 (1990).
31. V.V. Sinitsyn, L.M. Metlitscaya, A.G. Mamontova, G.A. Konovalov, V.V. Kukharchuk, Biomat. Artif. Cells. Artif. Organs, 18 (1990) 629.
32. B. Sellergren, J. Wieschemeyer, K.S. Boos, D. Seidel, Langmuir, 10 (1998) 4037.
33. H. Yu, G. Fu, B. He, Cellulose, 14 (2007) 99.
34. H. Yavuz, A. Denizli, J. Biomater. Sci. Polym. Ed., 14 (2003) 395.
35. H. Yavuz, A. Denizli, Macromol. Biosci., 5 (2005) 39.
36. H. Yavuz, V. Karakoç, D. Türkmen, R. Say, AA., Int. J. Biol. Macromol., 41 (2007) 8.
37. D. Silvestri, N. Barbani, M.L. Coluccio, C. Pegararo, P. Guisti, C. Cristallini, G. Ciardelli, Sep. Sci. Technol., 42 (2007) 2829.