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

Kyoon Kim Sang, Kwang Meyung Kim, Seulki Lee, Kyeongsoon Park, Hyung Park Jae, Ick Chan Kwon, Kuiwon Choi, Choong Yong Kim, Youngro Byun

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)861-870
Number of pages10
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume39
Issue number5
DOIs
Publication statusPublished - 2005 Oct 4
Externally publishedYes

Fingerprint

Desoxycorticosterone Acetate
Surface Plasmon Resonance
Surface plasmon resonance
Heparin
Brushes
Microvilli
Adhesion
Membranes
Deoxycholic Acid
Biosensing Techniques
Dimethyl Sulfoxide
Dextrans
Biosensors
Lysine
Amines
Rats

Keywords

  • Brush border membrane
  • Deoxycholic acid
  • Heparin
  • Surface plasmon resonance

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science

Cite this

Evaluation of absorption of heparin-DOCA conjugates on the intestinal wall using a surface plasmon resonance. / Sang, Kyoon Kim; Kim, Kwang Meyung; Lee, Seulki; Park, Kyeongsoon; Jae, Hyung Park; Kwon, Ick Chan; Choi, Kuiwon; Kim, Choong Yong; Byun, Youngro.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 39, No. 5, 04.10.2005, p. 861-870.

Research output: Contribution to journalArticle

Sang, Kyoon Kim ; Kim, Kwang Meyung ; Lee, Seulki ; Park, Kyeongsoon ; Jae, Hyung Park ; Kwon, Ick Chan ; Choi, Kuiwon ; Kim, Choong Yong ; Byun, Youngro. / Evaluation of absorption of heparin-DOCA conjugates on the intestinal wall using a surface plasmon resonance. In: Journal of Pharmaceutical and Biomedical Analysis. 2005 ; Vol. 39, No. 5. pp. 861-870.
@article{321ffabd037e43418dd26870237e0272,
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.",
keywords = "Brush border membrane, Deoxycholic acid, Heparin, Surface plasmon resonance",
author = "Sang, {Kyoon Kim} and Kim, {Kwang Meyung} and Seulki Lee and Kyeongsoon Park and Jae, {Hyung Park} and Kwon, {Ick Chan} and Kuiwon Choi and Kim, {Choong Yong} and Youngro Byun",
year = "2005",
month = "10",
day = "4",
doi = "10.1016/j.jpba.2005.06.014",
language = "English",
volume = "39",
pages = "861--870",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - Evaluation of absorption of heparin-DOCA conjugates on the intestinal wall using a surface plasmon resonance

AU - Sang, Kyoon Kim

AU - Kim, Kwang Meyung

AU - Lee, Seulki

AU - Park, Kyeongsoon

AU - Jae, Hyung Park

AU - Kwon, Ick Chan

AU - Choi, Kuiwon

AU - Kim, Choong Yong

AU - Byun, Youngro

PY - 2005/10/4

Y1 - 2005/10/4

N2 - 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.

AB - 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.

KW - Brush border membrane

KW - Deoxycholic acid

KW - Heparin

KW - Surface plasmon resonance

UR - http://www.scopus.com/inward/record.url?scp=26644447763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26644447763&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2005.06.014

DO - 10.1016/j.jpba.2005.06.014

M3 - Article

C2 - 16143485

AN - SCOPUS:26644447763

VL - 39

SP - 861

EP - 870

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 5

ER -