Diclofenac Enables Prolonged Delivery of Naltrexone Through Microneedle-Treated Skin
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The purpose of this study was to determine if non-specific COX inhibition could extend pore lifetime in hairless guinea pigs following microneedle treatment.
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.
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.
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.
KEY WORDScyclooxygenase microneedle micropore naltrexone
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.
- 5.Marie L, Foegh PWR. The eicosanoids: prostaglandins, thromboxanes, leukotrienes, & related compounds. In: Katzung BG, editor. Basic & clinical pharmacology. 9th ed. New York: McGraw-Hill; 2004. p. 298–312.Google Scholar
- 12.Banks SL, Pinninti RR, Gill HS, Paudel KS, Crooks PA, Brogden NK, Prausnitz MR, Stinchcomb AL. Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs. J Pharm Sci 2010;99(7):3072–80.Google Scholar
- 15.Banks S, Paudel K, Stinchcomb A, Loftin C. COX enzyme inhibitor enables drug delivery through microneedle treated skin for seven days. AAPS J. 2008;10(S2).Google Scholar
- 23.Valiveti S, Nalluri BN, Hammell DC, Paudel KS, Stinchcomb AL. Development and validation of a liquid chromatography-mass spectrometry method for the quantitation of naltrexone and 6beta-naltrexol in guinea pig plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;810(2):259–67.PubMedGoogle Scholar