Physicochemical conjugation with deoxycholic acid and dimethylsulfoxide for heparin oral delivery

Sang Kyoon Kim, June Huh, Sang Yoon Kim, Youngro Byun, Dong Yun Lee, Hyun Tae Moon

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Heparin, as therapeutic medications, cannot be administered orally because of its hydrophilic and high molecular weight. Here, we present a new technology to enhance the absorption of heparin in the intestine through its chemical conjugation with deoxycholic acid (DOCA) that can interact with bile acid transporter in the intestine. For the ampiphilic property and complete dissolution, the modified heparin was physically complexed with dimethylsulfoxide (DMSO). The DOCA-conjugated heparin could form nanoparticles in aqueous solution, whereas it was completely dissolved when treated with above 10% DMSO solution. Molecular dynamics computation study and two-dimensional homonulcear 1H nuclear overhauser effect spectroscopy (NOESY) NMR spectra demonstrated that one heparin molecule was chemically conjugated with two DOCA molecules that were physically interacted with six DMSO molecules within 4 Å via hydrophobic interactions and partly via hydrogen bonding. Its therapeutic efficacy was also pharmaceutically analyzed. When the DMSO-bound DOCA-conjugated heparin was orally administered into mice, its therapeutic efficacy was enhanced according to the amount of bound DMSO. Also, after oral administration of fluorescence-labeled DMSO-bound DOCA-conjugated heparin, it was circulated in the whole body for above 2 h. However, the DOCA-conjugated heparin without DMSO binding was fast eliminated after oral absorption. This study demonstrates that the interaction of structural constraints, DOCA and DMSO, with heparin can serve as a platform technology for potential macromolecule oral delivery.

Original languageEnglish
Pages (from-to)1451-1458
Number of pages8
JournalBioconjugate Chemistry
Volume22
Issue number7
DOIs
Publication statusPublished - 2011 Jul 20
Externally publishedYes

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Deoxycholic Acid
Dimethyl Sulfoxide
Heparin
Acids
Molecules
Intestines
Molecular Computers
Technology
Molecular Dynamics Simulation
Hydrogen Bonding
Macromolecules
Hydrophobic and Hydrophilic Interactions
Nanoparticles
Nuclear magnetic resonance spectroscopy
Oral Administration
Molecular dynamics
Hydrogen bonds
Dissolution
Magnetic Resonance Spectroscopy
Therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Physicochemical conjugation with deoxycholic acid and dimethylsulfoxide for heparin oral delivery. / Kim, Sang Kyoon; Huh, June; Kim, Sang Yoon; Byun, Youngro; Lee, Dong Yun; Moon, Hyun Tae.

In: Bioconjugate Chemistry, Vol. 22, No. 7, 20.07.2011, p. 1451-1458.

Research output: Contribution to journalArticle

Kim, Sang Kyoon ; Huh, June ; Kim, Sang Yoon ; Byun, Youngro ; Lee, Dong Yun ; Moon, Hyun Tae. / Physicochemical conjugation with deoxycholic acid and dimethylsulfoxide for heparin oral delivery. In: Bioconjugate Chemistry. 2011 ; Vol. 22, No. 7. pp. 1451-1458.
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