, Volume 68, Issue 4, pp 1128–1133 | Cite as

Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice

  • Jennifer Zhang
  • Yan Wang
  • Jane Y. Jin
  • Simone Degan
  • Russell P. Hall
  • Ryan D. Boehm
  • Panupong Jaipan
  • Roger J. NarayanEmail author


Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642-μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800-μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC.


Itraconazole Basal Cell Carcinoma National Comprehensive Cancer Network Imiquimod Polyglycolic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Gigi Davidson, Director of Clinical Pharmacy Services at the NC State College of Veterinary Medicine, and her staff for their efforts to develop and prepare the itraconazole formulation. We thank Paul Khavari and Anthony Oro of Stanford University for providing the SHH expression construct.


  1. 1.
    “Basal cell carcinoma” (The Skin Cancer Foundation, 2015), Accessed 4 January 2016.
  2. 2.
    S.V. Mohan and A.L.S. Chang, Curr. Dermatol. Rep. 3, 40 (2014).CrossRefGoogle Scholar
  3. 3.
    H.M. Gloster and K. Neal, J. Am. Acad. Dermatol. 55, 741 (2006).CrossRefGoogle Scholar
  4. 4.
    S. Wu, J. Han, W.Q. Li, T. Li, and A.A. Qureshi, Am. J. Epidemiol. 178, 890 (2013).CrossRefGoogle Scholar
  5. 5.
    M.R. Wehner, M.M. Chren, D. Nameth, A. Choudhry, M. Gaskins, K.T. Nead, W.J. Boscardin, and E. Linos, JAMA Dermatol. 150, 390 (2014).CrossRefGoogle Scholar
  6. 6.
    R. S. Bader, L. Santacroce, A. S. Kennedy, “Basal Cell Carcinoma Treatment & Management” (Medscape, 2016), Accessed 4 Jan 2016.
  7. 7.
    F. Bath-Hextall, M. Ozolins, S.J. Armstrong, G.B. Colver, W. Perkins, P.S. Miller, and H.C. Williams, Lancet Oncol. 15, 96 (2014).CrossRefGoogle Scholar
  8. 8.
    S.P. Shumack, Aust. Prescr. 34, 6 (2011).CrossRefGoogle Scholar
  9. 9.
    K. Korgavkar, E.F. Firoz, M. Xiong, R. Lew, K. Marcolivio, N. Burnside, R. Dyer, M.A. Weinstock, and VAKCC Trial Group, J. Cutan. Med. Surg. 18, 229 (2014).CrossRefGoogle Scholar
  10. 10.
    “Fluorouracil Cream” (, 2016), Accessed 4 Jan 2016.
  11. 11.
    “Aldara” (, 2016), Accessed 4 Jan 2016.
  12. 12.
    “Itraconazole” (Merck Sharp & Dohme Corp., 2016), Accessed 4 Jan 2016.
  13. 13.
    “Itraconazole”, (, 2016). Accessed 4 Jan 2016.
  14. 14.
    N. Mulcahy, “Common Antifungal Drug Works in Basal Cell Carcinoma” (Medscape, 2016) Accessed 4 Jan 2016.
  15. 15.
    J. Kim, J.Y. Tang, R.Y. Gong, J. Kim, J.J. Lee, K.V. Clemons, C.R. Chong, K.S. Chang, M. Fereshteh, D. Gardner, T. Reya, J.O. Liu, E.H. Epstein, D.A. Stevens, and P.A. Beachy, Cancer Cell 17, 388 (2010).CrossRefGoogle Scholar
  16. 16.
    L. Dirix, J. Clin. Oncol. 32, 720 (2014).CrossRefGoogle Scholar
  17. 17.
    J. Kim, B.T. Aftab, J.Y. Tang, D. Kim, A.H. Lee, M. Rezaee, J. Kim, B. Chen, E.M. King, A. Borodovsky, G.J. Riggins, E.H. Epstein, P.A. Beachy, and C.M. Rudin, Cancer Cell 23, 23 (2013).CrossRefGoogle Scholar
  18. 18.
    J. Montoya, M. Molgo, P. Uribe, and S. Gonzalez, J. Am. Acad. Dermatol. 66, AB155 (2012).Google Scholar
  19. 19.
    D.J. Kim, J. Kim, K. Spaunhurst, J. Montoya, R. Khodosh, K. Chandra, T. Fu, A. Gilliam, M. Molgo, P.A. Beachy, and J.Y. Tang, J. Clin. Oncol. 32, 745 (2014).CrossRefGoogle Scholar
  20. 20.
    D.J. Kim, J. Kim, K. Spaunhurst, J. Montoya, R. Khodosh, T. Fu, A. Gilliam, M. Molgo, P.A. Beachy, and J.Y. Tang, J. Invest. Dermatol. 582, S101 (2014).Google Scholar
  21. 21.
    “Sporanox & Lamisil Public Health Advisory issued.” (Medscape 2016), Accessed 4 Jan 2016.
  22. 22.
    F. Kesisoglou, S.Y. Zhou, S. Niemiec, J.W. Lee, E.M. Zimmermann, and D. Fleisher, Pharm. Res. 22, 1320 (2005).CrossRefGoogle Scholar
  23. 23.
    H. Hong, J. Sun, and W. Cai, Clin. Cosmet. Investig. Dermatol. 1, 1 (2008).Google Scholar
  24. 24.
    “Itraconazole” (Selleck Chemicals, 2016), Accessed 4 Jan 2016.
  25. 25.
    P. Khanna, J.A. Strom, J.I. Malone, and S. Bhansali, J. Diabetes Sci. Technol. 2, 1122 (2008).CrossRefGoogle Scholar
  26. 26.
    S.H. Baria, M.C. Gohel, T.A. Mehta, and O.P. Sharma, J. Pharmacol. Pharmacother. 64, 11 (2011).CrossRefGoogle Scholar
  27. 27.
    A. Arora, M. Prausnitz, and S. Mitragotri, Int. J. Pharm. 364, 227 (2008).CrossRefGoogle Scholar
  28. 28.
    H.S. Gill, D.D. Denson, B.A. Burris, and M.R. Prausnitz, Clin. J. Pain 24, 585 (2008).CrossRefGoogle Scholar
  29. 29.
    S.H. Bariya, M.C. Gohel, T.A. Mehta, and O.P. Sharma, J. Pharm. Pharmacol. 64, 11 (2011).CrossRefGoogle Scholar
  30. 30.
    Y.C. Kim, J.H. Park, and M.R. Prausnitz, Adv. Drug Deliver. Rev. 64, 1547 (2012).CrossRefGoogle Scholar
  31. 31.
    T.M. Tuan-Mahmood, M.T. McCrudden, B.M. Torrisi, E. McAlister, M.J. Garland, T.R. Singh, and R.F. Donnelly, Eur. J. Pharm. Sci. 50, 623 (2013).CrossRefGoogle Scholar
  32. 32.
    R.D. Boehm, J. Daniels, S. Stafslien, A. Nasir, J. Lefebvre, and R.J. Narayan, Biointerphases 10, 011004 (2015).CrossRefGoogle Scholar
  33. 33.
    J.H. Park, M.G. Allen, and M.R. Prausnitz, J. Control. Release 104, 51 (2005).CrossRefGoogle Scholar
  34. 34.
    V. V. Yuzhakov, Microneedle array, patch, and applicator for transdermal drug delivery, US Patent 7658728 B2, February 9, 2010.Google Scholar
  35. 35.
    V. V. Yuzhakov, Tissue conforming microneedle array and patch for transdermal drug delivery or biological fluid collection, US Patent 7785301 B2, August 31, 2010.Google Scholar
  36. 36.
    V. V. Yuzhakov, Method of making microneedle array and device for applying microneedle array to skin, US Patent US8414548 B2, April 9, 2013.Google Scholar
  37. 38.
    H. Fan, A.E. Oro, M.P. Scott, and P.A. Khavari, Nat. Med. 3, 788 (1997).CrossRefGoogle Scholar
  38. 37.
    R. D. Boehm, P. Jaipan, S. A. Skoog, S. Stafslien, L. Vanderwal, and R. J. Narayan, Biointerphases 11, 011008 (2016).CrossRefGoogle Scholar

Copyright information

© The Minerals, Metals & Materials Society 2016

Authors and Affiliations

  • Jennifer Zhang
    • 1
  • Yan Wang
    • 1
  • Jane Y. Jin
    • 1
  • Simone Degan
    • 1
    • 2
  • Russell P. Hall
    • 1
  • Ryan D. Boehm
    • 3
  • Panupong Jaipan
    • 3
  • Roger J. Narayan
    • 3
    Email author
  1. 1.Department of DermatologyDuke University Medical CenterDurhamUSA
  2. 2.Department of ChemistryDuke UniversityDurhamUSA
  3. 3.UNC/NCSU Joint Department of Biomedical EngineeringRaleighUSA

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