In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants
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AuthorLópez Jaramillo, Francisco Javier; Girón González, María Dolores; Salto González, Rafael; Hernández Mateo, Fernando; Santoyo González, Francisco
Cross-linked saccharidesHypercholesterolemiaBile acid sequestrantsCyclodextrinDextrinStarchDivinyl sulfone
López Jaramillo, F.J.; et al. In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants. Molecules, 20(3): 3716-3729 (2015). [http://hdl.handle.net/10481/36490]
SponsorshipFinancial Support was provided by Universidad de Granada in the frame of the Granada Research of Excellence Initiative on BioHealth (GREIB).
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.