Abstract
The key issues in the development of a microneedle patch as a tool for transdermal drug delivery are safety and delivery performance in addition to economical production. In this paper, novel fabrication methods for an inexpensive microneedle patch made of biocompatible polymer are reported, along with functional verifications for the fabricated microneedle patch through animal models. We combined the merits of in-line microneedles, i.e., easy and economical production, with the superior performance of two-dimensionally arrayed microneedles. One-dimensionally fabricated microneedles were assembled to make two-dimensionally arrayed patches to attain our goal. First, we fabricated strips with one-dimensionally arrayed microneedles through deep X-ray lithography on polymethylmethacrylate or another negative photoresist, SU-8, with sharply reduced exposure time. Second, we assembled microneedle strips to make two-dimensionally arrayed microneedles, which we utilized further for fabrication of molding masters. Finally, we prepared microneedle patches made of polycarbonate by hot embossing with these masters. We then demonstrated the actual delivery of exogenous materials through application on skin via animal experiments, and we found no detectable side effects such as inflammation or allergic reactions at the site of application.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
C.A. Akdis, M. Akdis, A. Trautmann, K. Blaser, Current Opin. Immunol. 12, 641–646 (2000)
E.W. Becker, W. Ehrfeld, P. Hagmann, Microelectron. Eng. 4, 35–56 (1986)
J.H. Braybrook, Biocompatiblility: Assessment of medical devices and materials, Wiley, New York, (1997)
M.B. Brown, G.P. Martin, S.A. Jones, F.K. Akomeah, Drug Deliv. 13, 175–187 (2006)
G. Cevc, Adv. Drug Deliver. Rev. 56, 675–711 (2004)
M. Cormier, B. Johnson, M. Ameri, K. Nyam, L. Libiran, D.D. Zhang, P. Daddona, J. Control. Release 97, 503–511 (2004)
P.G. Coulie, P. van der Bruggen, Curr. Opin. Immunol. 15, 131–137 (2003)
C. Cremers, F. Bouamrane, L. Singleton, R. Schenk, Microsyst. Technol. 7, 11–16 (2001)
S.E. Cross, M.S. Roberts, Curr. Drug Deliv. 1, 81–92 (2004)
S.P. Davis, B.J. Landis, Z.H. Adams, M.G. Allen, M.R. Prausnitz, J. Biochem. 37, 1155–1163 (2004)
K. Dell, R. Koesters, L. Gissmann, Int. J. Cancer 118, 364–372 (2006)
A.R. Denet, R. Vanbever, V. Préat, Adv. Drug Deliver. Rev. 56, 659–674 (2004)
A.G. Doukas, N. Kollias, Adv. Drug Deliver. Rev. 56, 559–579 (2004)
H.S. Gill, M.R. Prausnitz, J. Control, Release 117, 227–237 (2007)
M. Han, D.H. Hyun, H.H. Park, S.S. Lee, C.H. Kim, C.G. Kim, J. Micromech. Microeng. 17, 1184–1191 (2007)
E. Harlow, D. Lane, Antibodies: A laboratory manual, 2nd edn. (Cold Spring Harbor Laboratory, New York, 1988)
S. Henry, D.V. McAllister, M.G. Allen, M.R. Prausnitz, J. Pharm. Sci. 87, 922–925 (1998a)
S. Henry, D.V. McAllister, M.G. Allen, M.R. Prausnitz, in Proc. IEEE Conf. MEMS, pp. 494–498 (1998b)
L. Jian, Y.M. Desta, J. Goettert, M. Bednarzik, B. Loechel, J. Yoonyoung, G. Aigeldinger, V. Singh, G. Ahrens, G. Gruetzner, R. Ruhmann, R. Degen, in Proc. SPIE 4979, 394–401 (2003)
Y.N. Kalia, A. Naik, J. Garrison, R.H. Guy, Adv. Drug. Deliver. Rev. 56, 619–658 (2004)
K. Kang, M. Kubin, K.D. Cooper, S.R. Lessin, G. Trinchieri, A.H. Rook, J. Immunol. 156, 1402–1407 (1996)
Y.C. Kim, S.S. Lee, J. Micromech. Microeng. 18, 015006–015012 (2008)
W. Martanto, S.P. Davis, N.R. Holiday, J. Wang, H.S. Gill, M.R. Prausnitz, Pharm. Res. 21, 947–952 (2004)
D.V. McAllister, M.G. Allen, M.R. Prausnitz, Annu. Rev. Biomed. Eng. 2, 289–313 (2000)
D.V. McAllister, P.M. Wang, S.P. Davis, J.H. Park, P.J. Canatella, M.G. Allen, M.R. Prausnitz, Pro. Natl. Acad. Sci. USA 100, 13755–13760 (2003)
S.J. Moon, S.S. Lee, J. Micromech. Microeng. 15, 903–911 (2005)
S.J. Moon, C.Y. Jin, S.S. Lee, J. Phys.: Conference Series 34, 180–186 (2006)
J.H. Park, S. Davis, Y.K. Yoon, M.R. Prausnitz, M.G. Allen, in Proc. IEEE Conf. MEMS, pp. 371–374 (2003)
J.H. Park, M.G. Allen, M.R. Prausnitz, J. Control. Release 104, 51–66 (2005)
L.A. Pinto, J. Edwards, P.E. Castle, C.D. Harro, D.R. Lowy, J.T. Schiller, D. Wallace, W. Kopp, J.W. Adelsberger, M.W. Baseler, J.A. Berzofsky, A. Hildesheim, J. Exp. Med. 188, 327–338 (2003)
S.A. Plotkin, Nat. Med. Suppl. 11, S5–S11 (2005)
M.R. Prausnitz, S. Mitragotri, R. Langer, Nat. Rev. Drug Discov. 3, 115–124 (2004)
I. Roitt, J. Brostoff, D. Male, Immunology, 6th edn. (Harcourt, London, 2001)
N. Romani, S. Koide, M. Crowley, M. Witmer-Pack, A.M. Livingstone, C.G. Fathman, K. Inaba, R.M. Steinman, J. Exp. Med. 169, 1169–1178 (1989)
N. Romani, S. Holzmann, C.H. Tripp, F. Koch, P. Stoitzner, APMIS 111, 725–740 (2003)
W.R. Runyan, K.E. Bean, Semiconductor integrated circuit processing technology, Addison-Wesley, New York (1990)
S. Sugiyama, S. Khumpuang, G. Kawaguchi, J. Micromech. Microeng. 14, 1399–1404 (2004)
E. Touitou, Expert Opin. Biol. Th. 2, 723–733 (2002)
A. Trautmann, F. Heuck, C. Mueller, P. Ruther, O. Paul, in Proc. Transducers, pp. 1420–1423, (2005)
T.L. Whiteside, R.B. Herberman, Curr. Biol. 7, 704–710 (1995)
G. Widera, J. Johnson, L. Kim, L. Libiran, K. Nyam, P.E. Daddona, M. Cornier, Vaccine 24, 1653–1664 (2006)
A.C. Williams, B.W. Barry, Adv. Drug Deliver. Rev. 56, 603–618 (2004)
D.L. Woodland, Curr. Opin. Immunol. 15, 430–435 (2003)
Acknowledgments
The authors would like to thank the staff of 9C1 Deep Etch X-ray Lithography/White BeamLine, Pohang Light Source (PLS), Korea, and Korea Research Institute of Bioscience & Biotechnology (KRIBB) for their assistance with the fabrication process for microneedle patches and with the transdermal drug delivery experiment, respectively. This work was supported by the IT R&D program of MKE/IITA, Republic of Korea [2008-S-001-01, Ubiquitous Health Monitoring Module and System Development], and by the Center for Ultramicrochemical Process Systems sponsored by Korea Science and Engineering Foundation (KOSEF), Republic of Korea.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jin, C.Y., Han, M.H., Lee, S.S. et al. Mass producible and biocompatible microneedle patch and functional verification of its usefulness for transdermal drug delivery. Biomed Microdevices 11, 1195–1203 (2009). https://doi.org/10.1007/s10544-009-9337-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-009-9337-1