Number of the records: 1
Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP
- 1.
SYSNO ASEP 0370825 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP Author(s) Vávrová, K. (CZ)
Kovaříková, P. (CZ)
Školová, B. (CZ)
Líbalová, M. (CZ)
Roh, J. (CZ)
Čáp, R. (CZ)
Holý, Antonín (UOCHB-X)
Hrabálek, A. (CZ)Number of authors 8 Source Title Pharmaceutical Research. - : Springer - ISSN 0724-8741
Roč. 28, č. 12 (2011), s. 3105-3115Number of pages 11 s. Language eng - English Country US - United States Keywords acyclic nucleoside phosphonates ; antivirals ; antineoplastics ; permeation enhancer ; topical skin application ; transdermal delivery Subject RIV CC - Organic Chemistry R&D Projects 1M0508 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z40550506 - UOCHB-X (2005-2011) UT WOS 000297710200014 DOI 10.1007/s11095-011-0508-4 Annotation 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. In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin. Ability of 0.1-5% cPr-PMEDAP to cross human skin barrier was very low with flux values similar to 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 similar 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. 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2012
Number of the records: 1