Effect of Sulfated and Sulfonated Surfactants on the Intestinal Absorption of Heparin

Engel, Reto; Riggi, Stephen J.

doi:10.3181/00379727-130-33678

Cited by 21 publications

(7 citation statements)

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“…Engel and Riggi (70,71) studied the effect of surfactants on the intestinal absorption of heparin in the rat. They found that intraduodenal administration of heparin with either sodium lauryl sulfate, dioctyl sodium sulfosuccinate, or G-3300 (an alkyl aryl sulfonate) resulted in an increase in heparin absorption over that observed when heparin was administered alone.…”

Section: Factors Influencing Drug Permeation Of Biologic Membranesmentioning

confidence: 99%

Mechanisms of Surfactant Effects on Drug Absorption

Gibaldi

Feldman

1970

Journal of Pharmaceutical Sciences

190

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Section: Factors Influencing Drug Permeation Of Biologic Membranesmentioning

confidence: 99%

Mechanisms of Surfactant Effects on Drug Absorption

Gibaldi

Feldman

1970

Journal of Pharmaceutical Sciences

190

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“…Research into drug delivery through the paracellular route dates back to the 1960s, with the development of absorption enhancers [15,16]. Absorption enhancers are either calcium chelators or surfactants [17]; both act by modulating the epithelial barrier [18].…”

Section: Introductionmentioning

confidence: 99%

Tight Junction Modulators: Promising Candidates for Drug Delivery

Kondoh¹,

Yagi

2007

CMC

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Recent advances in genomic drug development and high-throughput technologies, such as combinatorial chemistry, high throughput screening and in silico screening, are making it easier to screen compounds with pharmaceutical activity. Drugs developed by genomic and throughput technologies traverse the epithelial and endothelial membranes. Although the paracellular pathway is a potent drug delivery route for these drugs, few strategies for their delivery have been developed because tight junctions (TJs), which exist between adjacent cells, strictly regulate the movement of solutes. Recent progress in biology of TJs has provided new insights into the biochemical and functional structure of TJs, and into the roles that occludin, claudins and tricellulin play in regulating TJ barriers. Novel strategies based on TJ-components for delivering drugs through the paracellular pathway have been developed. In this review, we discuss drug delivery through the paracellular route within the context of biology of TJs, as well as future directions of TJ-component-based drug delivery systems.

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“…A variety of agents, including EDTA and acidic buffer, were used to enhance the absorption of heparin. We and others have used sulfonated and nonsulfonated surfactants which facilitated the absorption of the drug; however, there were some toxic effects on the gut mucosa [2][3][4][5]. The use of bile acids, which are natural surfactants, was successfully developed by our group for the rectal and oral administration of insulin [6,7] and we were able to show that sodium cholate (Sch), in concentrations which are physiologically found in the intestinal tract, facilitated transmucosal absorption of insulin.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Absorption of Low Molecular Weight Heparin in Animals and Human Subjects

Nissan

Ziv²,

Kidron

et al. 2000

Pathophysiol Haemos Thromb

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Introduction: We had previously shown that the use of bile salts, which act as surfactants, facilitates the intestinal absorption of large molecules such as those of heparin and insulin. However, the bioavailability of unfractionated heparin (UFH) administered through the large intestine was low. The aim of the present study was to evaluate the absorption of low molecular weight heparin (LMWH) combined with bile salts through the gut mucosa in animals and human subjects. Materials and Methods: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH with or without sodium cholate (Sch) was administrated rectally in rats and healthy volunteers via a microenema. Absorption was estimated by the activated partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the plasma lipoprotein lipase (LPL) activation. Results: In groups of 6 rats, LMWH at doses of 100–1,000 U with sodium cholate (10–20 mg/ml) was readily absorbed through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1 U/ml and a dose-dependent activation of LPL. The absorption was significantly superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The plasma anti-factor Xa levels in the 6 healthy volunteers who received a microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15 min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also observed in these subjects. The plasma LMWH levels after rectal application were in the same range as those obtained after subcutaneous administration, however the elimination time (t½) was shorter. There were no adverse reactions. Conclusions: Intestinal absorption of LMWH facilitated by Sch is both feasible and safe. A slow release formulation will be needed to prolong the plasma half-life.

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Effect of Sulfated and Sulfonated Surfactants on the Intestinal Absorption of Heparin

Cited by 21 publications

References 0 publications

Mechanisms of Surfactant Effects on Drug Absorption

Mechanisms of Surfactant Effects on Drug Absorption

Tight Junction Modulators: Promising Candidates for Drug Delivery

Intestinal Absorption of Low Molecular Weight Heparin in Animals and Human Subjects

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