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Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs
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SYSNO ASEP 0427788 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs Author(s) Diblíková, D. (CZ)
Kopečná, M. (CZ)
Školová, B. (CZ)
Krečmerová, Marcela (UOCHB-X) RID, ORCID
Roh, J. (CZ)
Hrabálek, A. (CZ)
Vávrová, K. (CZ)Number of authors 7 Source Title Pharmaceutical Research. - : Springer - ISSN 0724-8741
Roč. 31, č. 4 (2014), s. 1071-1081Number of pages 11 s. Language eng - English Country US - United States Keywords acyclic nucleoside phosphonate antivirals ; lysolipid prodrug ; penetration enhancer ; skin absorption ; transdermal drug delivery Subject RIV FR - Pharmacology ; Medidal Chemistry Institutional support UOCHB-X - RVO:61388963 UT WOS 000333080100019 EID SCOPUS 84897097799 DOI 10.1007/s11095-013-1228-8 Annotation In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin. The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin. The ability of ANPs to cross the human skin barrier was very low (0.5-1.4 nmol/cm(2)/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2 +/- 2.3 nmol/cm(2)/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption. By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery. 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 2015
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