title: Design, Synthesis, and Therapeutic Evaluation of Poly(acrylic acid)-tetraDOCA Conjugate as a Bile Acid Transporter Inhibitor.
abstract: Regulation of cholesterol and bile acid homeostasis has been attracting attention as a pharmaceutical target for the treatment of diseases, such as hypercholesterolaemia and type 2 diabetes. In recent years, small bile acid analogues have been developed for the purpose of apical sodium-dependent bile acid transporter (ASBT) inhibition. Here, we designed a novel hydrophilic ASBT inhibitor using oligomeric bile acid with a high affinity with ASBT. Polyacrylic acid-tetraDOCA conjugates (PATD) have the ability to bind to ASBT in order to induce hypocholesterolemic effects. Both the viability and the functionality of PATD were evaluated in vitro, showing that PATDs were effective in inhibiting the increases of cholesterol in the blood and oil in the liver induced by high fat diet (HFD). The results indicated that the newly developed biomaterials with oligomeric bile acids and a hydrophilic polymer are potent therapeutic agents for hyperlipidemia.
authors.forename: Jooho
authors.initials: J
authors.lastname: Park
authors.affiliation: ‡Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
authors.forename: Taslim A
authors.initials: TA
authors.lastname: Al-Hilal
authors.affiliation: §College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Jeong uk
authors.initials: Ju
authors.lastname: Choi
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004285:Dogs; D015195:Drug Design; D005951:Glucose Tolerance Test; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056004:Molecular Dynamics Simulation; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000180:Acrylic Resins; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; C006903:carbopol 940; D002784:Cholesterol