title: Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans.
abstract: OBJECTIVE
  Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans.
  
  
  METHODS
  Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application.
  
  
  RESULTS
  Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 h in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores).
  
  
  CONCLUSIONS
  This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
authors.forename: Stan L
authors.initials: SL
authors.lastname: Banks
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D004008:Diclofenac / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008845:Microinjections / Q000379:methods; D009271:Naltrexone / Q000008:administration & dosage* / Q000097:blood; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000097:blood; D009339:Needles; D012869:Skin Absorption / Q000187:drug effects; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D004008:Diclofenac; D009271:Naltrexone