title: Diclofenac delays micropore closure following microneedle treatment in human subjects.
abstract: Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance-time curve (AUC) was calculated. AUC was significantly higher at MN+diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions.
authors.affiliation: University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Bio-Pharm Building, 789 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Milewski
authors.forename: Priyanka
authors.initials: P
authors.lastname: Ghosh
authors.forename: Lucia
authors.initials: L
authors.lastname: Hardi
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 / Q000008:administration & dosage / Q000493:pharmacokinetics; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D058266:Dielectric Spectroscopy; D005260:Female; D006801:Humans; D008297:Male; D008845:Microinjections; D008875:Middle Aged; D009339:Needles; D016062:Porosity; D012867:Skin / Q000737:chemistry*; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac