Ammonium and Guanidinium Functionalized Hydrogels as Bile Acid Sequestrants: Synthesis, Characterization, and Biological Properties

Abstract

Novel cationic polymers as bile acid sequestrants (BAS) have been considered to be an attractive long-term therapy for the treatment of hypercholesterolemia. Due to the poor in vivo efficacy of the first generation of BAS like cholestyramine and colestipol, there is a need for discovering new generations of potent BAS. As part of our polymeric drug discovery efforts, we have developed a facile route to prepare functional hydrogels bearing pendant amine and guanidinium groups. The polymeric amines were prepared either by direct polymerization of amine containing monomers or by chemical modification of suitable polymeric precursors. Polymers bearing guanidinium groups were obtained by a polymer analog reaction on crosslinked polymeric amines (primary or secondary) using a readily available guanylating agent in aqueous medium. Incorporation of guanidinium groups to these polymers occurs under mild reaction condition. A numbers of polymer structures with pendant amine and guanidinium groups located at varying distances from the polymer backbone were obtained. These ORDER REPRINTS polymeric ammonium and guanidinium salts were evaluated in vivo as BAS and hence cholesterol lowering agents.

Cyanobiphenyl versus Alkoxybiphenyl: Which Mesogenic Unit Governs the Mesomorphic Properties of Guanidinium Ionic Liquid Crystals?

“…[1][2][3][4][5] With high thermal stability, the ease of charge delocalization and coordination properties as well as the possibility to attach up to six different substituents on the guanidine moiety has driven research activities in diverse directions, resulting in their use as superbases, [6,7] ligands for coordination complexes, [8][9][10][11] organocatalysts, [12][13][14][15][16] stimuli-responsive materials, [17] hydrogels, [18] anion exchange polymer electrolytes for fuel cells, [19] and biologically active compounds [20][21][22][23][24][25][26][27][28][29] for drug development. Furthermore, guanidinium salts have also entered the field of ionic liquid crystals (ILCs) [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] as an alternative cationic head group to the imidazolium-derived ILCs, which have dominated this research area so far.…”

Polymeric bile acid sequestrants—Synthesis using conventional methods and new approaches based on “controlled”/living radical polymerization

“…The cationic groups ensure the occurrence of electrostatic interactions with the ionized bile acids, the more efficient being usually based on the ammonium group [14,38]. Other cationic groups, such as guanidinium have been tested but have shown poorer results [38]. The polymers hydrophobic segments are used to attract the steroid skeleton of bile acid molecules.…”