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Molecularly Imprinted Bile Acid Sequestrants: Synthesis and Biological Studies

Published online by Cambridge University Press:  01 February 2011

Chad C. Huval ,
Xi Chen ,
S. Randall Holmes-Farley ,
W. Harry Mandeville ,
Steven C. Polomoscanik ,
Robert J. Sacchiero  and
Pradeep K. Dhal
Chad C. Huval
Affiliation:
Genzyme Corporation, Drug Discovery and Development, 153 Second Avenue, Waltham, MA 02451, U.S.A.
Xi Chen
Affiliation:
Genzyme Corporation, Drug Discovery and Development, 153 Second Avenue, Waltham, MA 02451, U.S.A.
Steven C. Polomoscanik
Affiliation:
Genzyme Corporation, Drug Discovery and Development, 153 Second Avenue, Waltham, MA 02451, U.S.A.
Robert J. Sacchiero
Affiliation:
Genzyme Corporation, Drug Discovery and Development, 153 Second Avenue, Waltham, MA 02451, U.S.A.
Pradeep K. Dhal
Affiliation:
Genzyme Corporation, Drug Discovery and Development, 153 Second Avenue, Waltham, MA 02451, U.S.A.
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Abstract

Novel bile acid sequestrants based on a polyammonium backbone were synthesized using molecular imprinting technique. These imprinted polymer networks were prepared by crosslinking different polymeric amines with crosslinking agents in the presence of sodium cholate as the template. The template molecules were completely removed from the polymer matrices by repeated washings. The bile acid sequestration properties of these polymeric resins were evaluated under both in vitro and in vivo conditions. Adsorption isotherms performed in physiologically relevant media revealed that molecular imprinting led to improvement in bile acid sequestration with about a twofold increase in the Ka (association constant). More importantly, hamsters fed with imprinted polymers in their diet excreted more bile acids than the non-imprinted control polymer. These results suggest that molecular imprinting may be potentially an interesting approach to prepare novel polymer therapeutics.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 787: Symposium G – Molecularly Imprinted Materials , 2003 , G6.3
Copyright
Copyright © Materials Research Society 2004

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References

REFERENCES

1. Brown, M. S. and Goldstein, J. L., Proc. Natl. Acad. Sci. USA, 96, 11041 (1999).Google Scholar
2. Grundy, S. M., Am. J. Cardiology, 70, 271 (1992).Google Scholar
3. Stedronsk y, E. R., Biochim. et Biophys. Acta, 1210, 255 (1994).Google Scholar
4. Mandeville, W. H. and Goldberg, D. I., Current Pharmaceutical Design, 3, 15 (1997).Google Scholar
5. Zarras, P. and Vogl, O., Prog. Polym. Sci. 24, 485 (1999).Google Scholar
6. Sellergren, B. (Ed.) Molecularly Imprinted Polymers: Man-made Mimetics of Antibodies and Their Application in Analytical Chemistry, Elsevier, Amsterdam, 2000.Google Scholar
7. Dhal, P. K., Holmes-Farley, S. R., Mandeville, W. H. and Neenan, T. X. in Encyclopedia of Polymer Science and Technology, 3rd Edition, Markowitz, J. (Ed), John Wiley & Sons, New York (in press).Google Scholar
8. Harada, S. and Hasegawa, S., Makromol. Chem. Rapid Commun., 5, 27 (1984).Google Scholar
9. Mandeville, W. H, Braulin, W., Dhal, P., Guo, A., Huval, C., Miller, K., Petersen, J., Polomoscanik, S., Rosenbaum, D., Sacchiero, R., Ward, J. and Holmes-Farley, S. R., Mat. Res. Soc. Symp. Proc., 550, 3 (1999).Google Scholar
10. Huval, C. C., Bailey, M. J., Holmes-Farley, S. R., Mandeville, W. H., Miller-Gilmore, K., Sacchiero, R. J., and Dhal, P. K., J. Macromol. Sci. Pure. Appl. Chem. A38, 1559 (2001).Google Scholar
11. Nair, P. P. and Kritchevsky, D. (Eds), The Bile Acids: Chemistry, Physiology and Medicine, Plenum Publishing, New York, 1971.Google Scholar