Pharmaceutical Research

, Volume 28, Issue 12, pp 3105–3115 | Cite as

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

  • Kateřina Vávrová
  • Petra Kovaříková
  • Barbora Školová
  • Martina Líbalová
  • Jaroslav Roh
  • Robert Čáp
  • Antonín Holý
  • Alexandr Hrabálek
Research Paper



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 ~40 ng/cm2/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.


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.


acyclic nucleoside phosphonates antineoplastics antivirals permeation enhancer topical skin application transdermal delivery 



N 6 -cyclopropyl-2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine


dodecyl 6-dimethylaminohexanoate


Hanks balanced salt solution


phosphate-buffered saline







This work was supported by the Centre for New Antivirals and Antineoplastics (1M0508), the Czech Science Foundation (207/11/0365), Ministry of Education of the Czech Republic (MSM0021620822), and Charles University (SVV-2010-263-001). We also thank Dr. Ivan Votruba for a sample of cPr-PMEDAP and helpful comments on this manuscript, and Dr. Dana Prochazkova (Sigma-Aldrich) for the gift of the AscentisTM RP-Amide HPLC column.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kateřina Vávrová
    • 1
    • 2
    • 6
  • Petra Kovaříková
    • 3
  • Barbora Školová
    • 2
  • Martina Líbalová
    • 2
  • Jaroslav Roh
    • 2
  • Robert Čáp
    • 4
  • Antonín Holý
    • 5
  • Alexandr Hrabálek
    • 1
    • 2
  1. 1.Centre for New Antivirals and Antineoplastics Faculty of Pharmacy in Hradec KrálovéCharles University in PragueHradec KrálovéCzech Republic
  2. 2.Department of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec KrálovéCharles University in PragueHradec KrálovéCzech Republic
  3. 3.Department of Pharmaceutical Chemistry and Drug Control Faculty of Pharmacy in Hradec KrálovéCharles University in PragueHradec KrálovéCzech Republic
  4. 4.Clinics of Surgery, University HospitalHradec KrálovéCzech Republic
  5. 5.Centre for New Antivirals and AntineoplasticsInstitute of Organic Chemistry & Biochemistry AS CR, v.v.i.PragueCzech Republic
  6. 6.Charles University in Prague, Faculty of Pharmacy Hradec KrálovéHradec KrálovéCzech Republic

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