Evaluation of absorption of heparin-DOCA conjugates on the intestinal wall using a surface plasmon resonance

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 39; no. 5; pp. 861 - 870
• Main Authors: Kim, Sang Kyoon, Kim, Kwangmeyung, Lee, Seulki, Park, Kyeongsoon, Park, Jae Hyung, Kwon, Ick Chan, Choi, Kuiwon, Kim, Choong-Yong, Byun, Youngro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.10.2005; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Animals; Anticoagulants - chemistry; Anticoagulants - pharmacokinetics; Anticoagulants - pharmacology; Biological and medical sciences; Blood Coagulation - drug effects; Brush border membrane; Carbohydrate Sequence; Deoxycholic acid; Deoxycholic Acid - chemistry; Deoxycholic Acid - pharmacokinetics; Deoxycholic Acid - pharmacology; Dimethyl Sulfoxide - pharmacokinetics; Duodenum - chemistry; Duodenum - metabolism; Fundamental and applied biological sciences. Psychology; General pharmacology; Heparin; Heparin - chemistry; Heparin - pharmacokinetics; Heparin - pharmacology; Intestinal Absorption - physiology; Intestinal Mucosa - chemistry; Intestinal Mucosa - metabolism; Light; Magnetic Resonance Spectroscopy; Medical sciences; Microcomputers; Microvilli - chemistry; Microvilli - metabolism; Molecular Sequence Data; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Scattering, Radiation; Spectroscopy, Fourier Transform Infrared; Surface plasmon resonance; Surface Plasmon Resonance - methods; Brush border membrane; Surface plasmon resonance; Heparin; Deoxycholic acid; Evaluation; Digestive system; Gut; Anticoagulant; Brush border; Absorption; Glycosaminoglycan; Pharmacokinetics; Conjugated compound
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2005.06.014

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.