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

Kim, Sang Kyoon; Kim, Kwangmeyung; Lee, Seulki; Park, Kyeongsoon; Park, Jae Hyung; Kwon, Ick Chan; Choi, Kuiwon; Kim, Choong-Yong; Byun, Youngro

doi:10.1016/j.jpba.2005.06.014

Cited by 29 publications

(27 citation statements)

References 32 publications

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“…The chemically modified heparin derivative LHD had either the increased liphophilicity or the interaction between the conjugated DOCA molecules and bile acid transporters in the intestine, thereby enabling oral absorption. In the previous study, we experimentally showed the direct interaction between LHD and ileal brush border membrane surface by using the surface plasmon resonance technique and the increased liphophilicity and partition coefficient (K O/W ) in the octanol/water solution of LHD (18,19). In addition, LHD was actually absorbed efficiently in monkeys and mice at clinical acceptable doses.…”

Section: Discussionmentioning

confidence: 96%

Antimetastatic Effect of an Orally Active Heparin Derivative on Experimentally Induced Metastasis

Lee

Park

Kim

et al. 2008

Clinical Cancer Research

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Purpose: Orally active anticancer drugs have great advantages for the treatment of cancer.Compelling data suggest that heparin exhibits critical antimetastatic effects via interference with P-selectin^mediated cell-cell binding. However, heparin should be given parenterally because it is not orally absorbed. Here, we evaluated the inhibitory effect of orally absorbable heparin derivative (LHD) on experimentally induced metastasis. Experimental Design: We developed LHD, which is a chemical conjugate of low molecular weight heparin and deoxycholic acid, and measured the plasma concentration of LHD after oral administration. To evaluate the antimetastatic effect of LHD, we carried out experimental lung metastasis assays in vivo using murine melanoma or human lung carcinoma cells and interruption assay between murine melanoma cells and activated platelets and human umbilical vascular endothelial cells in vitro. Results: In mice, the plasma concentration was f7 Ag/mL at 20 minutes after oral administration of LHD (10 mg/kg), indicating that bleeding was not induced at this dose. Interestingly, we found that LHD dramatically attenuated metastasis experimentally induced by murine melanoma or human lung carcinoma cells and that its antimetastatic activity was attributed to the interruption of the interactions between melanoma cells and activated platelets and between melanoma cells and human umbilical vascular endothelial cells by blocking selectin-mediated interactions. Furthermore, it prevented tumor growth in secondary organs. Conclusions: On the basis of these findings, the present study shows the possibility of LHD as a suitable first-line anticancer drug that can be used for preventing metastasis and recurrence because it has therapeutic potential as an antimetastatic drug, has lower side effects, and can be orally absorbed.

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Section: Discussionmentioning

confidence: 96%

Antimetastatic Effect of an Orally Active Heparin Derivative on Experimentally Induced Metastasis

Lee

Park

Kim

et al. 2008

Clinical Cancer Research

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“…The chemically modified heparin derivative, LHD, had the increased liphophilicity due to the hydrophobic DOCA, thereby increasing the passive penetration through the mucous layer in the intestine wall. In addition, the chemically conjugated DOCA can interact with bile acid transporters that are highly expressed in the ileum, thereby enabling the transportermediated active penetration (25)(26)(27). In our previous study, we experimentally showed the direct interaction between LHD and ileal brush border membrane (BBM) surface by using surface Plasmon resonance technique (27).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the chemically conjugated DOCA can interact with bile acid transporters that are highly expressed in the ileum, thereby enabling the transportermediated active penetration (25)(26)(27). In our previous study, we experimentally showed the direct interaction between LHD and ileal brush border membrane (BBM) surface by using surface Plasmon resonance technique (27). Also, from the mechanism studies of LHD absorption using Caco-2 cell monolayers for mimicking the intestine, we demonstrated that LHD highly permeated by passive diffusion through the transcellular route, and its permeation was partially affected by bile acid transporters (26).…”

Section: Discussionmentioning

confidence: 99%

“…LHD was prepared as described previously (26)(27)(28)(29). In brief, it was synthesized by conjugating the amine group of DOCA-NH 2 with the carboxylic groups of LMWH (Fraxiparin®, average MW 4.5 kDa; GlaxoSmithKline, Brentford, Middlesex, UK).…”

Section: Synthesis Of Orally Absorbable Heparin Derivative (Lhd)mentioning

confidence: 99%

“…We found that this new heparin derivative could be orally absorbable in the rodent and monkey with therapeutic efficacy (25,26). The oral absorption of heparin derivative was attributed to the conjugated DOCA molecule constituent, which could promote intestinal absorption by enhancing the hydrophobic properties of heparin and by increasing the interaction between heparin and the intestinal membrane (26,27). Interestingly, we demonstrated that chronic administration of the orally absorbable LHD can prevent cancer progression without adverse effects of heparin, suggesting the potential therapeutic efficacy of LHD as a new oral anticancer agent (28,29).…”

Section: Introductionmentioning

confidence: 95%

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Antiangiogenic Activity of Orally Absorbable Heparin Derivative in Different Types of Cancer Cells

Lee

Kim

et al. 2009

Pharm Res

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Survey of the year 2005 commercial optical biosensor literature

2006

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We identified 1113 articles (103 reviews, 1010 primary research articles) published in 2005 that describe experiments performed using commercially available optical biosensors. While this number of publications is impressive, we find that the quality of the biosensor work in these articles is often pretty poor. It is a little disappointing that there appears to be only a small set of researchers who know how to properly perform, analyze, and present biosensor data. To help focus the field, we spotlight work published by 10 research groups that exemplify the quality of data one should expect to see from a biosensor experiment. Also, in an effort to raise awareness of the common problems in the biosensor field, we provide side-by-side examples of good and bad data sets from the 2005 literature.

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

Cited by 29 publications

References 32 publications

Antimetastatic Effect of an Orally Active Heparin Derivative on Experimentally Induced Metastasis

Antimetastatic Effect of an Orally Active Heparin Derivative on Experimentally Induced Metastasis

Antiangiogenic Activity of Orally Absorbable Heparin Derivative in Different Types of Cancer Cells

Survey of the year 2005 commercial optical biosensor literature

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