title: In vitro delivery of novel, highly potent anti-varicella zoster virus nucleoside analogues to their target site in the skin.
abstract: OBJECTIVE
  To determine the in-vitro dermal delivery of a new class of lipophilic, highly potent and uniquely selective anti-VZV nucleoside analogues in comparison with aciclovir.
  
  
  METHODS
  Three test compounds (Cf1698, Cf1743, Cf1712) and aciclovir were formulated into propylene glycol/aqueous cream BP formulations and finite doses applied to full-thickness pig ear skin for 48 hours in vertical Franz-type diffusion cells. Receptor phase samples were taken at specific intervals to determine permeation, and depth profiles were constructed following tape stripping and membrane separation.
  
  
  RESULTS
  All three test compounds reached the target basal epidermis in concentrations suggesting they would be highly efficacious in reducing viral load. Furthermore, the data showed that each of the test compounds would perform in a far superior manner to aciclovir, the current treatment of choice.
  
  
  CONCLUSIONS
  The dermatomal site of viral replication during secondary infection--the basal epidermis--was successfully targeted. Topical delivery of these compounds is highly promising as a new first line treatment of VZV infections. By attacking the virus at the first sign of reactivation, it is proposed that the extent of damage caused by the virus would be significantly lowered, thereby limiting the extent and severity of post-herpetic neuralgia.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Jarvis
authors.forename: Chris
authors.initials: C
authors.lastname: McGuigan
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000254:growth & development; D009705:Nucleosides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009824:Ointments / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D011741:Pyrimidine Nucleosides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D006113:United Kingdom
chemical_list: D000998:Antiviral Agents; C500966:Cf 1698; C500968:Cf 1712; C500967:Cf 1743; D009705:Nucleosides; D009824:Ointments; D019999:Pharmaceutical Solutions; D011741:Pyrimidine Nucleosides; D013535:Suspensions; D000212:Acyclovir