Diclofenac delays micropore closure following microneedle treatment in human subjects

Nicole K Brogden; Mikolaj Milewski; Priyanka Ghosh; Lucia Hardi; Leslie J Crofford; Audra L Stinchcomb

doi:10.1016/j.jconrel.2012.08.015

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Diclofenac delays micropore closure following microneedle treatment in human subjects

Journal article

Open access

Peer reviewed

Diclofenac delays micropore closure following microneedle treatment in human subjects

Nicole K Brogden, Mikolaj Milewski, Priyanka Ghosh, Lucia Hardi, Leslie J Crofford and Audra L Stinchcomb

Journal of controlled release, Vol.163(2), pp.220-229

10/28/2012

DOI: 10.1016/j.jconrel.2012.08.015

PMCID: PMC3725617

PMID: 22929967

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https://www.ncbi.nlm.nih.gov/pmc/articles/3725617View

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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. [Display omitted]

Human

Clinical

Transdermal

Micropore

Microneedle

Diclofenac

Details

Title: Subtitle: Diclofenac delays micropore closure following microneedle treatment in human subjects
Creators: Nicole K Brogden - University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Bio-Pharm Building, 789 South Limestone Street, Lexington, KY 40536, USA
Mikolaj Milewski - University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Bio-Pharm Building, 789 South Limestone Street, Lexington, KY 40536, USA
Priyanka Ghosh - University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Bio-Pharm Building, 789 South Limestone Street, Lexington, KY 40536, USA
Lucia Hardi - University of Kentucky, Department of Internal Medicine, Lexington, KY, 740 S. Limestone St., J509 Kentucky Clinic, Lexington, KY 40536, USA
Leslie J Crofford - University of Kentucky, Department of Internal Medicine, Lexington, KY, 740 S. Limestone St., J509 Kentucky Clinic, Lexington, KY 40536, USA
Audra L Stinchcomb - University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Bio-Pharm Building, 789 South Limestone Street, Lexington, KY 40536, USA
Resource Type: Journal article
Publication Details: Journal of controlled release, Vol.163(2), pp.220-229
DOI: 10.1016/j.jconrel.2012.08.015
PMID: 22929967
PMCID: PMC3725617
NLM abbreviation: J Control Release
ISSN: 0168-3659
eISSN: 1873-4995
Publisher: Elsevier B.V
Language: English
Date published: 10/28/2012
Academic Unit: Dermatology; Pharmaceutical Sciences and Experimental Therapeutics; Physical Therapy and Rehabilitation Science
Record Identifier: 9984025308202771

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