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Diclofenac Enables Unprecedented Week-Long Microneedle-Enhanced Delivery of a Skin Impermeable Medication in Humans

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Abstract

Purpose

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).

Conclusion

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.

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Abbreviations

COX:

Cyclooxygenase

MN:

Microneedle

NTX:

Naltrexone

NTXol:

Naltrexol

SC:

Stratum corneum

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Acknowledgments and Disclosures

We would like to acknowledge Dr. Mark Prausnitz and Dr. Vladimir Zarnitsyn (Georgia Institute of Technology) for their expertise regarding the MNs and impedance measurements, and the staff at the UK Center for Clinical and Translational Science for their assistance. This work was funded by the following NIH grants: CTSA 1UL1RR033173-01, R01DA13425, R42DA32191, 1F31DA029374, and the Clinical Loan Repayment Program. Other funding included the UK Center for Clinical and Translational Science Seed Grant.

Dr. Stinchcomb is the Chief Scientific Officer of AllTranz Inc., a specialty pharmaceutical company involved in the development of transdermal formulations for microneedle delivery; both she and Dr. Banks are significant shareholders in the company.

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Author notes

  1. Nicole K. Brogden

    Present address: Department of Pharmaceutical Sciences & Experimental Therapeutics, The University of Iowa College of Pharmacy, Iowa City, Iowa, USA

  2. Audra L. Stinchcomb

    Present address: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine Street, Baltimore, Maryland, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA

    Nicole K. Brogden & Audra L. Stinchcomb

  2. AllTranz Inc.,, Lexington, Kentucky, USA

    Stan L. Banks & Audra L. Stinchcomb

  3. Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA

    Leslie J. Crofford

Authors
  1. Nicole K. Brogden
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  2. Stan L. Banks
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  3. Leslie J. Crofford
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  4. Audra L. Stinchcomb
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Corresponding author

Correspondence to Audra L. Stinchcomb.

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Brogden, N.K., Banks, S.L., Crofford, L.J. et al. Diclofenac Enables Unprecedented Week-Long Microneedle-Enhanced Delivery of a Skin Impermeable Medication in Humans. Pharm Res 30, 1947–1955 (2013). https://doi.org/10.1007/s11095-013-1036-1

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  • DOI: https://doi.org/10.1007/s11095-013-1036-1

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