title: Oral delivery of taurocholic acid linked heparin-docetaxel conjugates for cancer therapy.
abstract: We have synthesized taurocholic acid (TCA) linked heparin-docetaxel (DTX) conjugates for oral delivery of anticancer drug. The ternary biomolecular conjugates formed self-assembly nanoparticles where docetaxel was located inside the core and taurocholic acid was located on the surface of the nanoparticles. The coupled taurocholic acid in the nanoparticles had enhanced oral absorption, presumably through the stimulation of a bile acid transporter of the small intestine. The oral absorption profile demonstrated that the concentration of the conjugates in plasma is about 6 fold higher than heparin alone. An anti-tumor study in MDA-MB231 and KB tumor bearing mice showed significant tumor growth inhibition activity by the ternary biomolecular conjugates. Ki-67 histology study also showed evidence of anticancer activity of the nanoparticles. Finally, noninvasive imaging using a Kodak Molecular Imaging System demonstrated that the nanoparticles were accumulated efficiently in tumors. Thus, this approach for oral delivery using taurocholic acid in the ternary biomolecular conjugates is promising for treatment of various types of cancer.
authors.affiliation: Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea.
authors.forename: Zehedina
authors.initials: Z
authors.lastname: Khatun
authors.forename: Md
authors.initials: M
authors.lastname: Nurunnabi
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Reeck
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Cho
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013656:Taurocholic Acid / Q000008:administration & dosage* / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006495:Heparin, Low-Molecular-Weight; D043823:Taxoids; D000077143:Docetaxel; D013656:Taurocholic Acid