Skip to main content

Advertisement

SpringerLink
Log in

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

  • Research Article
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Transdermal delivery of therapeutic agents for cosmetic therapy is limited to small and lipophilic molecules by the stratum corneum barrier. Microneedle technology overcomes this barrier and offers a minimally invasive and painless route of administration. DermaRoller®, a commercially available handheld device, has metal microneedles embedded on its surface which offers a means of microporation. We have characterized the microneedles and the microchannels created by these microneedles in a hairless rat model, using models with 370 and 770 μm long microneedles. Scanning electron microscopy was employed to study the geometry and dimensions of the metal microneedles. Dye binding studies, histological sectioning, and confocal microscopy were performed to characterize the created microchannels. Recovery of skin barrier function after poration was studied via transepidermal water loss (TEWL) measurements, and direct observation of the pore closure process was investigated via calcein imaging. Characterization studies indicate that 770 μm long metal microneedles with an average base width of 140 μm and a sharp tip with a radius of 4 μm effectively created microchannels in the skin with an average depth of 152.5 ± 9.6 μm and a surface diameter of 70.7 ± 9.9 μm. TEWL measurements indicated that skin regains it barrier function around 4 to 5 h after poration, for both 370 and 770 μm microneedles. However, direct observation of pore closure, by calcein imaging, indicated that pores closed by 12 h for 370 μm microneedles and by 18 h for 770 μm microneedles. Pore closure can be further delayed significantly under occluded conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Wermeling DP, Banks SL, Hudson DA, Gill HS, Gupta J, Prausnitz MR, 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  PubMed  CAS  Google Scholar 

  2. Guy RH, Kalia YN, Delgado-Charro MB, Merino V, Lopez A, Marro D. Iontophoresis: electrorepulsion and electroosmosis. J Control Release. 2000;64(1–3):129–32.

    Article  PubMed  CAS  Google Scholar 

  3. Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Advanced drug delivery reviews. 2004;56(5):619–58.

    Article  PubMed  CAS  Google Scholar 

  4. Lee JW, Park JH, Prausnitz MR. Dissolving microneedles for transdermal drug delivery. Biomaterials. 2008;29(13):2113–4.

    Article  PubMed  CAS  Google Scholar 

  5. Mitragotri S, Blankschtein D, Langer R. Ultrasound-mediated transdermal protein delivery. Science. 1995;269(5225):850–3.

    Article  PubMed  CAS  Google Scholar 

  6. Paliwal S, Mitragotri S. Ultrasound-induced cavitation: applications in drug and gene delivery. Expert opinion on drug delivery. 2006;3(6):713–26.

    Article  PubMed  CAS  Google Scholar 

  7. Prausnitz MR. Microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56(5):581–7.

    Article  PubMed  CAS  Google Scholar 

  8. Prausnitz MR, Bose VG, Langer R, Weaver JC. Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery. Proc Natl Acad Sci U S A. 1993;90(22):10504–8.

    Article  PubMed  CAS  Google Scholar 

  9. Vemulapalli V, Yang Y, Friden PM, Banga AK. Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate. J Pharm Pharmacol. 2008;60(1):27–33.

    Article  PubMed  CAS  Google Scholar 

  10. Banga AK. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies. Boca Raton: CRC; 2011.

    Book  Google Scholar 

  11. Kaushik S, Hord AH, Denson DD, McAllister DV, Smitra S, Allen MG, et al. Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001;92(2):502–4.

    Article  PubMed  CAS  Google Scholar 

  12. Haq MI, Smith E, John DN, Kalavala M, Edwards C, Anstey A, et al. Clinical administration of microneedles: skin puncture, pain and sensation. Biomed Microdevices. 2009;11(1):35–47.

    Article  PubMed  CAS  Google Scholar 

  13. Gill HS, Denson DD, Burris BA, Prausnitz MR. Effect of microneedle design on pain in human volunteers. Clin J Pain. 2008;24(7):585–94.

    Article  PubMed  Google Scholar 

  14. Donnelly RF, Singh TR, Tunney MM, Morrow DI, McCarron PA, O’Mahony C, et al. Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro. Pharm Res. 2009;26(11):2513–2.

    Article  PubMed  CAS  Google Scholar 

  15. Birchall JC, Clemo R, Anstey A, John DN. Microneedles in clinical practice—an exploratory study into the opinions of healthcare professionals and the public. Pharm Res. 2011;28(1):95–106.

    Article  PubMed  CAS  Google Scholar 

  16. Doddaballapur S. Microneedling with DermaRoller. J Cutan Aesthet Surg. 2009;2(2):110–1.

    Article  PubMed  Google Scholar 

  17. Majid I. Microneedling therapy in atrophic facial scars: an objective assessment. J Cutan Aesthet Surg. 2009;2(1):26–30.

    Article  PubMed  Google Scholar 

  18. Fabbrocini G, Fardella N, Monfrecola A, Proietti I, Innocenzi D. Acne scarring treatment using skin needling. Clin Exp Dermatol. 2009;34(8):874–9.

    Article  PubMed  CAS  Google Scholar 

  19. Leheta T, El Tawdy A, Abdel Hay R, Farid S. Percutaneous collagen induction versus full-concentration trichloroacetic acid in the treatment of atrophic acne scars. Dermatol Surg. 2011;37(2):207–16.

    Article  PubMed  CAS  Google Scholar 

  20. Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87(8):922–5.

    Article  PubMed  CAS  Google Scholar 

  21. Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res. 2008;25(1):104–13.

    Article  PubMed  CAS  Google Scholar 

  22. Uhoda E, Pierard-Franchimont C, Debatisse B, Wang X, Pierard G. Repair kinetics of the stratum corneum under repeated insults. Exog Dermatol. 2004;3(1):7–11.

    Article  Google Scholar 

  23. Li G, Badkar A, Nema S, Kolli CS, Banga AK. In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int J Pharm. 2009;368(1–2):109–15.

    Article  PubMed  CAS  Google Scholar 

  24. Kalluri H, Banga AK. Formation and closure of microchannels in skin following microporation. Pharm Res. 2011;28(1):82–94.

    Article  PubMed  CAS  Google Scholar 

  25. Badran MM, Kuntsche J, Fahr A. Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. Eur J Pharm Sci. 2009;36(4–5):511–23.

    Article  PubMed  CAS  Google Scholar 

  26. Coulman SA, Birchall JC, Alex A, Pearton M, Hofer B, O’Mahony C, 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  PubMed  CAS  Google Scholar 

  27. Menon GK, Feingold KR, Elias PM. Lamellar body secretory response to barrier disruption. J Invest Dermatol. 1992;98(3):279–89.

    Article  PubMed  CAS  Google Scholar 

  28. Ahn SK, Jiang SJ, Hwang SM, Choi EH, Lee JS, Lee SH. Functional and structural changes of the epidermal barrier induced by various types of insults in hairless mice. Arch Dermatol Res. 2001;293(6):308–18.

    Article  PubMed  CAS  Google Scholar 

  29. Kennish L, Reidenberg B. A review of the effect of occlusive dressings on lamellar bodies in the stratum corneum and relevance to transdermal absorption. Dermatol Online J. 2005;11(3):7.

    PubMed  Google Scholar 

  30. Jiang S, Koo SW, Lee SH. The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane. Arch Dermatol Res. 1998;290(3):145–51.

    Article  PubMed  CAS  Google Scholar 

  31. Gupta J, Andrews S, Gill H, Prausnitz M. Kinetics of skin resealing after insertion of microneedles in human subjects. The 35th Annual Meeting and Exposition of the Controlled Release Society; July 19–22, 2008.

  32. Banks SL, Paudel KS, Brogden NK, Loftin CD, Stinchcomb AL. Diclofenac enables prolonged delivery of naltrexone through microneedle-treated skin. Pharm Res. 2011;28:1211–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, Georgia, 30341, USA

    Haripriya Kalluri & Ajay K. Banga

  2. California Northstate College of Pharmacy, Rancho Cordova, California, 95670, USA

    Chandra Sekhar Kolli

Authors
  1. Haripriya Kalluri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chandra Sekhar Kolli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ajay K. Banga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ajay K. Banga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalluri, H., Kolli, C.S. & Banga, A.K. Characterization of Microchannels Created by Metal Microneedles: Formation and Closure. AAPS J 13, 473–481 (2011). https://doi.org/10.1208/s12248-011-9288-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-011-9288-3

Key words

Search

Navigation