Enhanced topical and transdermal delivery of antineoplastic and antiviral acyclic nucleoside phosphonate cPr-PMEDAP
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- adenin aplikace a dávkování MeSH
- antitumorózní látky aplikace a dávkování MeSH
- antivirové látky aplikace a dávkování MeSH
- aplikace kožní MeSH
- dimethylaminy MeSH
- dodekanol MeSH
- kapronáty metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kůže metabolismus MeSH
- lidé MeSH
- methylaminy metabolismus MeSH
- organofosfonáty aplikace a dávkování MeSH
- permeabilita MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenin MeSH
- antitumorózní látky MeSH
- antivirové látky MeSH
- dimethylaminy MeSH
- dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
- dodekanol MeSH
- kapronáty MeSH
- methylaminy MeSH
- N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Prohlížeč
- organofosfonáty MeSH
PURPOSE: Acyclic nucleoside phosphonates possess unique antiviral and antineoplastic activities; however, their polar phosphonate moiety is associated with low ability to cross biological membranes. We explored the potential of transdermal and topical delivery of 2,6-diaminopurine derivative cPr-PMEDAP. METHODS: In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin. RESULTS: Ability of 0.1-5% cPr-PMEDAP to cross human skin barrier was very low with flux values ~40 ng/cm(2)/h, the majority of compound found in the stratum corneum. The highest permeation rates were found at pH 6; increased donor concentration had no influence. The permeation enhancer dodecyl 6-dimethylaminohexanoate (DDAK, 1%) increased flux of cPr-PMEDAP (up to 61 times) and its concentration in nucleated epidermis (up to ~0.5 mg of cPr-PMEDAP/g of the tissue). No deamination of cPr-PMEDAP into PMEG occurred during permeation studies, but N-dealkylation into PMEDAP mediated by skin microflora was observed. CONCLUSIONS: Transdermal or topical application of cPr-PMEDAP enabled by the permeation enhancer DDAK may provide an attractive alternative route of administration of this potent antitumor and antiviral compound.
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