title: Evaluation of absorption of heparin-DOCA conjugates on the intestinal wall using a surface plasmon resonance.
abstract: We validated the application of the surface plasmon resonance (SPR) technique to reliably determine adhesion of drugs to the intestinal wall using heparin-DOCA conjugates, developed to enhance the oral absorption of poorly absorbed heparin. In this study, heparin conjugates, or deoxycholyl-heparin (H-DOCA) and bisdeoxycholyl-heparin (H-bis-DOCA), were synthesized by covalently coupling the synthesized succinimido deoxycholate (DOCA-NHS) or succinimido bis-deoxycholyl-L-lysine (DOCA-bis-NHS) to amine groups of heparin, and their physicochemical and biological properties were evaluated. To mimic the duodenal and ileal surfaces, duodenal and ileal brush border membrane (BBM) vesicles isolated from Sprauge-Dawley (SD) rats were immobilized onto a biosensor chip composed of dextran derivatives with modified lipophilic residues. The adhesion of heparin conjugates on the BBM surface was evaluated by measuring the SPR response signal. The adhesion of heparin conjugates was significantly dependent on the conjugated DOCA molecules: that is, they showed higher adhesion signal on the ileal BBM surface than that on the duodenal BBM surface. In particular, the solubilized heparin conjugates in DMSO solution presented significantly increased adhesion affinity on the ileal BBM surface. The adhesion of heparin conjugates on the intestinal surfaces was successfully assayed using the surface plasmon resonance technique with the sensor chip on which BBM vesicles were immobilized.
authors.affiliation: Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 1 Oryong-dong Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Sang Kyoon
authors.initials: SK
authors.lastname: Kim
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Choong-Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002240:Carbohydrate Sequence; D003840:Deoxycholic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000493:pharmacokinetics; D004386:Duodenum / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008838:Microcomputers; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D017550:Spectroscopy, Fourier Transform Infrared; D020349:Surface Plasmon Resonance / Q000379:methods*
chemical_list: D000925:Anticoagulants; D003840:Deoxycholic Acid; D006493:Heparin; D004121:Dimethyl Sulfoxide