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An electrically active microneedle array for electroporation

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Abstract

We have designed and fabricated a microneedle array with electrical functionality with the final goal of electroporating skin’s epidermal cells to increase their transfection by DNA vaccines. The microneedle array was made of polymethylmethacrylate (PMMA) by micromolding technology from a polydimethylsiloxane (PDMS) mold, followed by metal deposition, patterning using laser ablation, and electrodeposition. This microneedle array possessed sufficient mechanical strength to penetrate human skin in vivo and was also able to electroporate both red blood cells and human prostate cancer cells as an in vitro model to demonstrate cell membrane permeabilization. A computational model to predict the effective volume for electroporation with respect to applied voltages was constructed from finite element simulation. This study demonstrates the mechanical and electrical functionalities of the first MEMS-fabricated microneedle array for electroporation, designed for DNA vaccine delivery.

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References

  • H. Aihara, J. Miyazaki, Nat. Biotechnol. 16, 867 (1998)

    Article  Google Scholar 

  • B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Molecular biology of the cell, 4th edn. (Garland Science, New York, 2002), p. 627

    Google Scholar 

  • S. Aparicio, R. Alcalde, Green Chem. 11, 65 (2009)

    Article  Google Scholar 

  • S. Babiuk, M.E. Baca-Estrada, M. Foldvari, M. Storms, D. Rabussay, G. Widera, L.A. Babiuk, Vaccine 20, 3399 (2002)

    Article  Google Scholar 

  • H. Becker, C. Gartner, Anal. Bioanal. Chem. 390, 89 (2008)

    Article  Google Scholar 

  • P.J. Canatella, J.F. Karr, J.A. Petros, M.R. Prausnitz, Biophys. J. 80, 755 (2001)

    Article  Google Scholar 

  • Y. Choi, M. McClain, M. LaPlaca, A. Frazier, M.G. Allen, Biomed. Microdevices 9, 7 (2007)

    Article  Google Scholar 

  • A.I. Daud, R.C. DeConti, S. Andrews, P. Urbas, A.I. Riker, V.K. Sondak, P.N. Munster, D.M. Sullivan, K.E. Ugen, J.L. Messina, R. Heller, J. Clin. Oncol. 26, 5896 (2008)

    Article  Google Scholar 

  • J.J. Donnelly, B. Wahren, M.A. Liu, J. Immunol. 175, 633 (2005)

    Google Scholar 

  • H.S. Gill, M.R. Prausnitz, J. Control. Release 117, 227 (2007)

    Article  Google Scholar 

  • H.S. Gill, D.D. Denson, B.A. Burris, M.R. Prausnitz, Clin. J. Pain 24, 585 (2008)

    Article  Google Scholar 

  • G.M. Glenn, R.T. Kenney, L.R. Ellingsworth, S.A. Frech, S.A. Hammond, J.P. Zoeteweij, Expert Rev. Vaccines 2, 253 (2003)

    Article  Google Scholar 

  • A. Gothelf, L.M. Mir, J. Gehl, Cancer Treat. Rev. 29, 371 (2003)

    Article  Google Scholar 

  • P. Griss, P. Enoksson, H.K. Tolvanen-Laakso, P. Meriläinen, S. Ollmar, G. Stemme, J. Microelectromech. S. 10, 10 (2001)

    Article  Google Scholar 

  • J.W. Hooper, J.W. Golden, A.M. Ferro, A.D. King, Vaccine 25, 1814 (2007)

    Article  Google Scholar 

  • M.J. Jaroszeski, R. Heller, R. Gilbert, Electrochemotherapy, electrogenetherapy, and transdermal drug delivery, 1st edn. (Humana, Totowa, 2000), pp. 1–4

    Google Scholar 

  • A.D. King, R.E. Walters, U.S. Patent No. 6,603,998 (2003)

  • P.E. Laurent, S. Bonnet, P. Alchas, P. Regolini, J.A. Mikszta, R. Pettis, N.G. Harvey, Vaccine 25, 8833 (2007)

    Article  Google Scholar 

  • M.A. Liu, J. Intern. Med. 253, 402 (2003)

    Article  Google Scholar 

  • S. Mehier-Humbert, R.H. Guy, Adv. Drug Deliver. Rev. 57, 733 (2005)

    Article  Google Scholar 

  • H. Mekid, L.M. Mir, Biochim. Biophys. Acta 1524, 118 (2000)

    Google Scholar 

  • L.M. Mir, S. Orlowski, J. Belehradek, J. Teissie, M.P. Rols, G. Sersa, D. Miklavčič, R. Gilbert, R. Heller, Bioelectroch. Bioener. 38, 203 (1995)

    Article  Google Scholar 

  • S. Mitragotri, Nat. Rev. Immunol. 5, 905 (2005)

    Article  Google Scholar 

  • Y. Mouneimne, P.F. Tosi, R. Barhoumi, C. Nicolau, Biochim. Biophys. Acta 1027, 53 (1990)

    Article  Google Scholar 

  • T. Niidome, L. Huang, Gene Ther. 9, 1647 (2002)

    Article  Google Scholar 

  • J.-H. Park, M.G. Allen, M.R. Prausnitz, J. Control. Release 104, 51 (2005)

    Article  Google Scholar 

  • I.Y. Park, Z.Y. Li, X.M. Li, A.P. Pisano, R.S. Williams, Biosens. Bioelectron. 22, 2065 (2007)

    Article  Google Scholar 

  • M.R. Prausnitz, Adv. Drug Deliver. Rev. 18, 395 (1996)

    Article  Google Scholar 

  • M.R. Prausnitz, R. Langer, Nat. Biotechnol. 26, 1261 (2008)

    Article  Google Scholar 

  • M.R. Prausnitz, V.G. Bose, R. Langer, J.C. Weaver, P. Natl. Acad. Sci. USA 90, 10504 (1993a)

    Article  Google Scholar 

  • M.R. Prausnitz, B.S. Lau, C.D. Milano, S. Conner, R. Langer, J.C. Weaver, Biophys. J. 65, 414 (1993b)

    Article  Google Scholar 

  • M.R. Prausnitz, J.A. Mikszta, M. Cormier, A.K. Andrianov, Curr. Top. Microbiol. Immunol. 333, 369 (2009)

    Article  Google Scholar 

  • G.J. Prud’homme, Y. Glinka, A.S. Khan, R. Draghia-Akli, Curr. Gene Ther. 6, 243 (2006)

    Article  Google Scholar 

  • J. Rice, C.H. Ottensmeier, F.K. Stevenson, Nat. Rev. Cancer 8, 108 (2008)

    Article  Google Scholar 

  • P.J. Rousche, D.S. Pellinen, D.P. Pivin, J.C. Williams, R.J. Vetter, D.R. Kipke, IEEE T. Biomed. Eng. 48, 361 (2001)

    Article  Google Scholar 

  • A. Sale, W. Hamilton, Biochim. Biophys. Acta 148, 781 (1967)

    Google Scholar 

  • S.L. Tao, T.A. Desai, Adv. Mater. 17, 1625 (2005)

    Article  Google Scholar 

  • I.M. Verma, M.D. Weitzman, Annu. Rev. Biochem. 74, 711 (2005)

    Article  Google Scholar 

  • J.C. Weaver, IEEE T. Plasma Sci. 20, 24 (2000)

    Article  Google Scholar 

  • G. Widera, J. Johnson, L. Kim, L. Libiran, K. Nyam, P.E. Daddona, M. Cormier, Vaccine 24, 1653 (2006)

    Article  Google Scholar 

  • A.C. Williams, Transdermal and topical drug delivery, 1st edn. (Pharmaceutical, London, 2003), pp. 5–14

    Google Scholar 

  • L. Zhang, E. Nolan, S. Kreitschitz, D.P. Rabussay, Biochim. Biophys. Acta 1572, 1 (2002)

    Google Scholar 

  • Q.Y. Zhu, V.G. Zarnitsyn, L. Ye, Z.Y. Wen, Y.L. Gao, L. Pan, I. Skountzou, H.S. Gill, M.R. Prausnitz, C.L. Yang, R.W. Compans, P. Natl. Acad. Sci. USA 106, 7968 (2009)

    Article  Google Scholar 

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Acknowledgements

This work was supported in part by National Institute of Health. The authors would like to thank Dr. Yoonsu Choi and Dr. Jin-Woo Park for helpful discussions regarding microneedle array fabrication. Mark Prausnitz and Mark Allen are inventors on patents owned by Georgia Tech that are relevant to this study. The associated conflict of interest is being managed by Georgia Tech.

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Correspondence to Mark R. Prausnitz or Mark G. Allen.

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Choi, SO., Kim, Y.C., Park, JH. et al. An electrically active microneedle array for electroporation. Biomed Microdevices 12, 263–273 (2010). https://doi.org/10.1007/s10544-009-9381-x

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