Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

0370825 - ÚOCHB 2012 RIV US eng J - Článek v odborném periodiku
Vávrová, K. - Kovaříková, P. - Školová, B. - Líbalová, M. - Roh, J. - Čáp, R. - Holý, Antonín - Hrabálek, A.
Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP.
Pharmaceutical Research. Roč. 28, č. 12 (2011), s. 3105-3115. ISSN 0724-8741. E-ISSN 1573-904X
Grant CEP: GA MŠMT 1M0508
Grant ostatní: GA ČR(CZ) GAP207/11/0365
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 4.093, rok: 2011

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.
Trvalý link: http://hdl.handle.net/11104/0006799