| Transdermal delivery of nitric oxide from diazeniumdiolates. | |
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MedLine Citation:
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PMID: 9685912 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adverse physiological effects can often interfere with the use of nitric oxide (NO) as a therapeutic agent, especially when it is systemically generated from prodrugs. NO which is generated and delivered site-specifically by transdermal donors may be useful in the treatment of parasitic, bacterial or viral skin infections without causing systemic side effects. Three diazeniumdiolates (formerly "NONOate"), including two water soluble compounds, (Z)-1-[N-2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1- ium-1,2-diolate (DETA-NO) and (Z)-1-[N-(3-aminopropyl)-N-(3-ammoniopropyl)amino] diazen-1-ium-1,2-diolate (DPTA-NO), and one insoluble compound, DPTA-NO grafted to dextran microspheres (DPTA-NO-g-dextran) were used to transdermally deliver NO to rats. Dextran microspheres were obtained by simultaneously grafting DPTA-NO to dextran and cross-linking dextran with CNBr in an oil-water emulsion. Suspended in hydrogel, DETA-NO, DPTA-NO, and DPTA-NO-g-dextran were applied three times to depilated rats at 4 day intervals. Results show that metabolic urinary nitrate levels increase with time (24-48 h), reach a maximum, and return to baseline by the fourth day. DPTA-NO applications produced an average maximum nitrate level of 94.2 mumol/day +/- 34.2 mumol S.D. compared to the average maximum nitrate level of 39.8 mumol/day +/- 8.6 mumol S.D. obtained from treatment with DETA-NO. These results suggest that DPTA-NO delivered NO more efficiently than DETA-NO. When DPTA-NO-g-dextran microspheres were used as the NO donor, results comparable to DPTA-NO were observed with an average maximum nitrate level of 14.9 mumol/day +/- 3.0 mumol S.D. These and other conclusive data indicate that, via these diazeniumdiolates, NO can be delivered effectively through rat skin. |
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Authors:
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D J Smith; M L Simmons |
Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of controlled release : official journal of the Controlled Release Society Volume: 51 ISSN: 0168-3659 ISO Abbreviation: J Control Release Publication Date: 1998 Feb |
Date Detail:
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Created Date: 1998-09-21 Completed Date: 1998-09-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 153-9 Citation Subset: IM |
Affiliation:
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Department of Chemistry, University of Akron, OH 44325-3601, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Cutaneous Animals Azetidines / administration & dosage, metabolism* Cross-Linking Reagents / chemistry Cyanogen Bromide / chemistry Dextrans / administration & dosage, chemistry, metabolism* Male Microspheres Nitrates / urine Nitric Oxide / administration & dosage*, urine Prodrugs / administration & dosage* Rats Rats, Sprague-Dawley Triazenes / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/1-(N-(3-aminopropyl)-N-(3-ammoniopropyl)amino)diazen-1-ium-1,2-diolate-dextran; 0/1-(N-(3-ammoniopropyl)-N-(n-propyl)amino)diazen-1-ium-1,2-diolate; 0/1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; 0/Azetidines; 0/Cross-Linking Reagents; 0/Nitrates; 0/Prodrugs; 0/Triazenes; 10102-43-9/Nitric Oxide; 506-68-3/Cyanogen Bromide; 9004-54-0/Dextrans |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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