An investigation of routes of administration of heparin other than injection

Windsor, E.; Freeman, Lucinda

doi:10.1016/0002-9343(64)90197-4

Cited by 21 publications

(13 citation statements)

References 21 publications

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“…polysaccharides [92]) and bacterial toxins [93]). In 1961, sodium EDTA (50 mg/kg) enabled absorption of heparin following oral administration in gelatin capsules to dogs [94]; three years later it was tested by rectal and sublingual delivery routes in man [95]. Since then, C 10 was approved in Scandinavia and Asia to improve rectal bioavailability of ampicillin from a suppository (Doktacillin TM , Meda Pharmaceuticals, Sweden), although the efficicay of this approach was correlated to non-specific damage to the rectal mucosae rather than paracellular permeability modification [83].…”

Section: Intestinal Pesmentioning

confidence: 99%

Section: Paracellular Pes That Target Occludinmentioning

confidence: 99%

“…Peptide sequences that correspond to the first extracellular loop motif of occludin (OP , OP and OP [90][91][92][93][94][95][96][97][98][99][100][101][102][103] ) can scramble homophilic interactions between adjacent epithelial cells and improve intestinal permeability [101]. However, even the shortest occludin peptide (OP [90][91][92][93][94][95][96][97][98][99][100][101][102][103] was only active when added bilaterally (68-fold benefit) or basolaterally (11-fold benefit) to epithelial monolayers on Transwells®. Efficacy (enzymatic/physical stability, targeting) of OP [90][91][92][93][94][95][96][97][98][99][100][101][102][103] was improved by synthesis of an all D-form, inclusion of peptidase inhibitors, and conjugation to a hydrocarbon moiety (C 14 -OP [90][91]...…”

Section: Paracellular Pes That Target Occludinmentioning

confidence: 99%

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Intestinal permeation enhancers for oral peptide delivery

Maher

Mrsny

Brayden

2016

Advanced Drug Delivery Reviews

270

201

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Publication informationAdvanced Drug Delivery Reviews, (Part B): 277-319 Publisher ElsevierItem record/more information http://hdl.handle.net/10197/7800Publisher's statement þÿ T h i s i s t h e a u t h o r s v e r s i o n o f a w o r k t h a t w a s a c c e p t e d f o r p u b l i c a t i o n i n A d v a n c e d D r u g Delivery Reviews. Changes resulting from the publishing process, such as peer review,

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Section: Intestinal Pesmentioning

confidence: 99%

Section: Paracellular Pes That Target Occludinmentioning

confidence: 99%

Section: Paracellular Pes That Target Occludinmentioning

confidence: 99%

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Intestinal permeation enhancers for oral peptide delivery

Maher

Mrsny

Brayden

2016

Advanced Drug Delivery Reviews

270

201

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“…Regardless of the route of administration, a simplified unifying principle for successful noninvasive macromolecular drug delivery may be to reversibly overcome the biological, biophysical, and biochemical barriers, and to safely and efficiently improve the in vivo spatial and temporal control of the drug to achieve a clinically acceptable therapeutic advantage . A comprehensive manuscript for alternative routes of heparin delivery, which covers limited routes of drug administration, was made by Windsor and Freeman in 1964 . Recently, a concise and comprehensive review on the importance and need of noninvasive delivery of heparins was published by Motlekar and Youan …”

Section: Parenteral Vs Noninvasive Delivery Of Heparinmentioning

confidence: 99%

Recent advances in search of oral heparin therapeutics

Paliwal

Paliwal²,

Agrawal³

et al. 2011

Medicinal Research Reviews

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Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are first choices of clinicians among available anticoagulants. Currently, these agents are administered either parenterally or subcutaneously, which reduces patient compliance and acceptability. Oral heparin may serve as an alternative to both parenteral heparin as well as presently available oral anticoagulants such as warfarin. This review focuses mainly upon recent perspectives in the development of heparin as an oral anticoagulant. The possibility of its success with special emphasis to nanotechnological approaches has been elaborated. Important strategies such as the use of penetration enhancers, the development of lipid conjugates of heparin, and the incorporation of heparin in polymeric matrix systems have been discussed. Additionally, introductory information on biological activities, physiochemical aspects, and pharmacokinetic and pharmacodynamic parameters of heparin is summarized. A brief comparison of UFH and LMWH is also included for reader's benefit. Informative discussion on clinical trials with the successes and limitations of oral heparin formulations is also presented. Overall, the present review provides complete insight to the research that has been carried out for the development of heparin as oral anticoagulant.

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“…The literature contains numerous reports of attempts to administer heparin orally (2)(3)(4), with little success in achieving clinically useful anticoagulant activity. Attempts have been made to improve enteral absorption in a number of ways: (i) use of adjuvants such as EDTA (5), citric acid (6), or dimethyl sulfoxide (7); (ii) oral administration in micellar solutions (8) or in liposomes (9); (iii) rectal administration with bile salts (10); or (iv) administration of low molecular weight heparins (4).…”

mentioning

confidence: 99%

Oral heparin results in the appearance of heparin fragments in the plasma of rats.

Larsen¹,

Lund²,

Langer³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fagments with cortisone [Folkman, J., Langer, R., Linhardt, R. J., Haudenschild, C. & Taylor, S. (1983) Science 221,[719][720][721][722][723][724][725]. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [35S]heparin or [3H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of "0.1 unit/ml. The radioactive material is Identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.We have previously demonstrated that the combination of heparin, or a heparin fragment, and cortisone inhibited angiogenesis, including the chicken chorioallantoic membrane and the rabbit corneal pocket assay (1). When the combination was used to inhibit tumor growth by parenteral administration to mice, a high rate of hemorrhagic complications was encountered because of the anticoagulant effect of heparin. Other methods of heparin administration were tried, and it was found that the anti-angiogenic effect was maintained when heparin was given orally even though the anticoagulant complications did not occur. This oral regimen inhibited tumor growth and metastasis in some animal tumor models. In an initial experiment to study the absorption of oral heparin, mice were given [35S]heparin in their drinking water. Serum obtained 24 hr later yielded 0.4% of the radioactivity that was present in the drinking water. However, gel filtration chromatography failed to demonstrate radiolabeled heparin fragments with biological activity (1).The anti-angiogenic activity of oral heparin was somewhat surprising. The literature contains numerous reports of attempts to administer heparin orally (2-4), with little success in achieving clinically useful anticoagulant activity. Attempts have been made to improve enteral absorption in a number of ways: (i) use of adjuvants such as EDTA (5), citric acid (6), or dimethyl sulfoxide (7); (ii) oral administration in micellar solutions (8) or in liposomes (9); (iii) rectal administration with bile salts (10); or (iv) administration of low molecular weight heparins (4). No such technique has yet achieved clinical usefulness.As a result of finding anti-angiogenic activity with oral heparin plus cortisone without anticoagulant activity, we decided to examine the fate of radiolabeled heparin given enterally. Furthermore, by examining two differently labeled heparins (35S and 3H), we sought to gain information about metabolism of the drug by desulfation and by depolymerization. We now show that a single oral dose of hepari...

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An investigation of routes of administration of heparin other than injection

Cited by 21 publications

References 21 publications

Intestinal permeation enhancers for oral peptide delivery

Intestinal permeation enhancers for oral peptide delivery

Recent advances in search of oral heparin therapeutics

Oral heparin results in the appearance of heparin fragments in the plasma of rats.

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