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.

• MeSH
• Adenine administration & dosage   MeSH
• Antiviral Agents administration & dosage   MeSH
• Administration, Cutaneous MeSH
• Dimethylamines MeSH
• Dodecanol MeSH
• Caproates metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Skin metabolism   MeSH
• Humans MeSH
• Methylamines metabolism   MeSH
• Organophosphonates administration & dosage   MeSH
• Permeability MeSH
• Swine MeSH
• Antineoplastic Agents administration & dosage   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenine MeSH
• Antiviral Agents MeSH
• Dimethylamines MeSH
• dodecyl 6-(dimethylamino)hexanoate MeSH Browser
• Dodecanol MeSH
• Caproates MeSH
• Methylamines MeSH
• N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Browser
• Organophosphonates MeSH
• Antineoplastic Agents MeSH