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Diclofenac Enables Prolonged Delivery of Naltrexone Through Microneedle-Treated Skin

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ABSTRACT

Purpose

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.

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ACKNOWLEDGMENTS

We would like to thank Dr. Harvinder Gill and Dr. Mark Prausnitz at the Georgia Institute of Technology for generously providing the MN arrays used for this work. This work was funded by NIH grant R01DA13425 and AllTranz Inc. ALS and SLB are significant shareholders in AllTranz, Inc., a specialty pharmaceutical company developing COX inhibitor technology for use with microneedles. AllTranz, Inc. and the University of Kentucky have pending patents for this technology.

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Authors and Affiliations

  1. AllTranz, Inc., Lexington, Kentucky, USA

    Stan L. Banks & Audra L. Stinchcomb

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 459 Wethington Bldg., 900 South Limestone Street, Lexington, Kentucky, 40536, USA

    Kalpana S. Paudel, Nicole K. Brogden, Charles D. Loftin & Audra L. Stinchcomb

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  1. Stan L. Banks
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  2. Kalpana S. Paudel
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  3. Nicole K. Brogden
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  4. Charles D. Loftin
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  5. Audra L. Stinchcomb
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Correspondence to Audra L. Stinchcomb.

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Banks, S.L., Paudel, K.S., Brogden, N.K. et al. Diclofenac Enables Prolonged Delivery of Naltrexone Through Microneedle-Treated Skin. Pharm Res 28, 1211–1219 (2011). https://doi.org/10.1007/s11095-011-0372-2

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  • DOI: https://doi.org/10.1007/s11095-011-0372-2

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