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Optimization of Impedance Spectroscopy Techniques for Measuring Cutaneous Micropore Formation after Microneedle Treatment in an Elderly Population

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ABSTRACT

Purpose

The objective of this study was to optimize a reproducible impedance spectroscopy method in elderly subjects as a means to evaluate the effects of microneedles on aging skin.

Methods

Human volunteers were treated with microneedles at six sites on the upper arm. Repeated impedance measurements were taken pre- and post-microneedle insertion. Two electrode types were evaluated (dry vs. gel), using either light or direct pressure to maintain contact between the electrode and skin surface. Transepidermal water loss (TEWL) was measured as a complementary technique.

Results

Five control subjects and nine elderly subjects completed the study. Microneedle insertion produced a significant decrease in impedance from baseline in all subjects (p < 0.05, regardless of electrode type or pressure application), confirming micropore formation. This was supported by a complementary significant increase in TEWL (p < 0.05). The gel*direct condition produced the lowest variability between measurements, as demonstrated by a coefficient of variation of 3.8% and 3.5% (control and elderly subjects, respectively). This was lower than variation between TEWL measurements at the same sites: 19.8% and 21.6% (control and elderly subjects, respectively).

Conclusions

Impedance spectroscopy reproducibly measures micropore formation in elderly subjects, which will be essential for future studies describing microneedle-assisted transdermal delivery in aging populations.

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Abbreviations

(CV%):

Coefficient of variation

(MN):

Microneedle

(SC):

Stratum corneum

(TEWL):

Transepidermal water loss

REFERENCES

  1. Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64(14):1547–68.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Wermeling DP et al. Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci U S A. 2008;105(6):2058–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Arora A, Prausnitz MR, Mitragotri S. Micro-scale devices for transdermal drug delivery. Int J Pharm. 2008;364(2):227–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Martanto W et al. Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004;21(6):947–52.

    Article  CAS  PubMed  Google Scholar 

  5. Pergolizzi J et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008;8(4):287–313.

    Article  PubMed  Google Scholar 

  6. Squier CA, et al. The effect of aging in oral mucosa and skin. 1994: CRC Press.

  7. Neerken S et al. Characterization of age-related effects in human skin: a comparative study that applies confocal laser scanning microscopy and optical coherence tomography. J Biomed Opt. 2004;9(2):274–81.

    Article  PubMed  Google Scholar 

  8. Curdy C et al. Non-invasive assessment of the effect of formulation excipients on stratum corneum barrier function in vivo. Int J Pharm. 2004;271(1–2):251–6.

    Article  CAS  PubMed  Google Scholar 

  9. Kalia YN, Guy RH. The electrical characteristics of human skin in-vivo. Pharm Res. 1995;12(11):1605–13.

    Article  CAS  PubMed  Google Scholar 

  10. Kawai E et al. Skin surface electric potential as an indicator of skin condition: a new, non-invasive method to evaluate epidermal condition. Exp Dermatol. 2008;17(8):688–92.

    Article  PubMed  Google Scholar 

  11. Gupta J et al. Kinetics of skin resealing after insertion of microneedles in human subjects. J Control Release. 2011;154(2):148–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Brogden NK et al. Development of in vivo impedance spectroscopy techniques for measurement of micropore formation following microneedle insertion. J Pharm Sci. 2013;102(6):1948–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Yamamoto T, Yamamoto Y. Electrical properties of the epidermal stratum corneum. Med Biol Eng. 1976;14(2):151–8.

    Article  CAS  PubMed  Google Scholar 

  14. Karande P, Jain A, Mitragotri S. Relationships between skin’s electrical impedance and permeability in the presence of chemical enhancers. J Control Release. 2006;110(2):307–13.

    Article  CAS  PubMed  Google Scholar 

  15. Lackermeier AH et al. In vivo ac impedance spectroscopy of human skin. Theory and problems in monitoring of passive percutaneous drug delivery. Ann N Y Acad Sci. 1999;873:197–213.

    Article  CAS  PubMed  Google Scholar 

  16. Brogden NK et al. Diclofenac delays micropore closure following microneedle treatment in human subjects. J Control Release. 2012;163(2):220–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Brogden NK et al. Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans. Pharm Res. 2013;30(8):1947–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Atkinson TJ et al. Medication pain management in the elderly: unique and underutilized analgesic treatment options. Clin Ther. 2013;35(11):1669–89.

    Article  PubMed  Google Scholar 

  19. Kaestli LZ et al. Use of transdermal drug formulations in the elderly. Drugs Aging. 2008;25(4):269–80.

    Article  CAS  PubMed  Google Scholar 

  20. Moxey ED et al. Prescription drug use in the elderly: a descriptive analysis. Health Care Financ Rev. 2003;24(4):127–41.

    PubMed  Google Scholar 

  21. Norman JJ et al. Microneedle patches: usability and acceptability for self-vaccination against influenza. Vaccine. 2014;32(16):1856–62.

    Article  PubMed  Google Scholar 

  22. Donnelly RF, et al. Hydrogel-forming microneedle arrays can be effectively inserted in skin by self-application: A pilot study centred on pharmacist intervention and a patient information leaflet. Pharm Res, 2014.

  23. Hoesly FJ et al. Safety of a novel microneedle device applied to facial skin: a subject- and rater-blinded, sham-controlled, randomized trial. Arch Dermatol. 2012;148(6):711–7.

    Article  PubMed  Google Scholar 

  24. Daddona PE et al. Parathyroid hormone (1–34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis. Pharm Res. 2011;28(1):159–65.

    Article  CAS  PubMed  Google Scholar 

  25. Brogden NK. Clinical evaluation of novel methods for extending microneedle pore lifetime. PhD Dissertation, University of Kentucky. (2012).

  26. Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28(3):321–6.

    Article  PubMed  Google Scholar 

  27. Donnelly RF et al. Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. J Control Release. 2010;147(3):333–41.

    Article  CAS  PubMed  Google Scholar 

  28. Coulman SA et al. In vivo, in situ imaging of microneedle insertion into the skin of human volunteers using optical coherence tomography. Pharm Res. 2011;28(1):66–81.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURE

We would like to thank Mark Prausnitz and Vladimir Zarnitsyn for their assistance with designing the MN arrays. This work was funded by the American Association of Colleges of Pharmacy (AACP) New Investigator Award, and the Executive Council for Graduate and Professional Studies Student Research Grant (University of Iowa).

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Correspondence to Nicole K. Brogden.

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Kelchen, M.N., Holdren, G.O., Farley, M.J. et al. Optimization of Impedance Spectroscopy Techniques for Measuring Cutaneous Micropore Formation after Microneedle Treatment in an Elderly Population. Pharm Res 31, 3478–3486 (2014). https://doi.org/10.1007/s11095-014-1435-y

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  • DOI: https://doi.org/10.1007/s11095-014-1435-y

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