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Molecules 2015, 20(3), 3716-3729; doi:10.3390/molecules20033716

In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants

1
Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Universidad de Granada, E18071 Granada, Spain
2
Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad de Granada, E18071 Granada, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Eduardo Sobarzo-Sánchez
Received: 18 November 2014 / Revised: 11 February 2015 / Accepted: 16 February 2015 / Published: 24 February 2015
View Full-Text   |   Download PDF [2680 KB, uploaded 24 February 2015]   |  

Abstract

Bile acid sequestrants (BAS) represent a therapeutic approach for the management of hypercholesterolemia that relies on the cationic polymeric nature of BAS to selectively bind negatively charged bile acids. We hypothesized that the cross-linking of β-cyclodextrin (β-CD) and saccharides such as starch or dextrin with divinyl sulfone (DVS) yields homo- and hetero-polymeric materials with the ability to trap sterols. Our hypothesis was put to test by synthesizing a library of 22 polymers that were screened to evaluate their capability to sequester both cholesterol (CHOL) and cholic and deoxycholic acids (CA and DCA). Three polymers synthesized in high yield were identified as promising. Two were neutral hetero-polymers of β-CD and starch or dextrin and the third was a weakly cationic homo-polymer of starch, highlighting the importance of the cavity effect. They were tested in hypercholesterolemic male Wistar rats and their ability to regulate hypercholesterolemia was similar to that for the reference BAS cholestyramine, but with two additional advantages: (i) they normalized the TG level and (ii) they did not increase the creatinine level. Neither hepatotoxicity nor kidney injury was detected, further supporting them as therapeutical candidates to manage hypercholesterolemia. View Full-Text
Keywords: cross-linked saccharides; hypercholesterolemia; bile acid sequestrants; cyclodextrin; dextrin; starch; divinyl sulfone cross-linked saccharides; hypercholesterolemia; bile acid sequestrants; cyclodextrin; dextrin; starch; divinyl sulfone
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lopez-Jaramillo, F.J.; Giron-Gonzalez, M.D.; Salto-Gonzalez, R.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants. Molecules 2015, 20, 3716-3729.

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