title: Diclofenac enables prolonged delivery of naltrexone through microneedle-treated skin.
abstract: OBJECTIVE
  The purpose of this study was to determine if non-specific COX inhibition could extend pore lifetime in hairless guinea pigs following microneedle treatment.
  
  
  METHODS
  Hairless guinea pigs were treated with microneedle arrays ± daily application of Solaraze® gel (3% diclofenac sodium (non-specific COX inhibitor) and 2.5% hyaluronic acid); transepidermal water loss was utilized to evaluate pore lifetime. To examine the permeation of naltrexone, additional guinea pigs were treated with microneedles ± daily Solaraze® gel followed by application of a 16% transdermal naltrexone patch; pharmacokinetic analysis of plasma naltrexone levels was performed. Histological analysis was employed to visualize morphological changes following microneedle and Solaraze® treatment.
  
  
  RESULTS
  Animals treated with microneedles + Solaraze® displayed extended pore lifetime (determined by transepidermal water loss measurements) for up to 7 days. Enhanced naltrexone permeation was also observed for an extended amount of time in animals treated with microneedles + Solaraze®. No morphological changes resulting from microneedle treatment or COX inhibition were noted.
  
  
  CONCLUSIONS
  Non-specific COX inhibition is an effective means of extending pore lifetime following microneedle treatment in hairless guinea pigs. This may have clinical implications for extending transdermal patch wear time and therefore increasing patient compliance with therapy.
authors.affiliation: AllTranz, Inc., Lexington, Kentucky, USA.
authors.forename: Stan L
authors.initials: SL
authors.lastname: Banks
authors.forename: Kalpana S
authors.initials: KS
authors.lastname: Paudel
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
authors.forename: Charles D
authors.initials: CD
authors.lastname: Loftin
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D006168:Guinea Pigs; D009271:Naltrexone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption / Q000187:drug effects*; D057968:Transdermal Patch
chemical_list: D016861:Cyclooxygenase Inhibitors; D009292:Narcotic Antagonists; D004008:Diclofenac; D009271:Naltrexone; D051545:Cyclooxygenase 1