title: Transdermal delivery and cutaneous targeting of antivirals using a penetration enhancer and lysolipid prodrugs.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Skin Barrier Research Group, Charles University in Prague Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 50005, Hradec Králové, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Diblíková
authors.forename: Monika
authors.initials: M
authors.lastname: Kopečná
authors.forename: Barbora
authors.initials: B
authors.lastname: Školová
authors.forename: Marcela
authors.initials: M
authors.lastname: Krečmerová
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Roh
authors.forename: Alexandr
authors.initials: A
authors.lastname: Hrabálek
authors.forename: Kateřina
authors.initials: K
authors.lastname: Vávrová
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000279:Administration, Cutaneous; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008081:Liposomes; D009924:Organ Culture Techniques; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D008081:Liposomes; D011355:Prodrugs; D015075:2-Aminopurine; C007300:2,6-diaminopurine