Abstract
This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.
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S.P. Davis, B.J. Landis, Z.H. Adams, M.G. Allen, M.R. Prausnitz, J. Biomech. 37, 1155–1163 (2004)
E.R. Edelman, P. Seifert, A. Groothuis, A. Morss, D. Bornstein, C. Rogers, Circulation 103(3), 429–434 (2001)
N. Fogh-Andersen, B.M. Altura, B.T. Altura, O. Siggaard-Andersen, Clin. Chem. 41(10), 1522–1525 (1995)
H.J.G.E. Gardeniers, R. Luttge, E.J.W. Berenschot, M.J. de Boer, S.Y. Yeshurun, M. Hefetz, R. van’t Oever, A. van den Berg, IEEE ASME J. Microelectromech. Syst. 12(6), 855–862 (2003)
P. Griss and G. Stemme, IEEE ASME J. Microelectromech. Syst. 12(3), 296–301 (2003)
K.M. Halparin, Br. J. Dermatol. 86(1), 14–19 (1972)
S. Henry, D. McAllister, M.G. Allen, M.R. Prausnitz, J. Pharm. Sci. 87, 922–925 (1998)
S. Kaushik, A.H. Hord, D.D. Denson, D.V. McAllister, S. Smitra, M.G. Allen, M.R. Prausnitz, Anesth. Analg. 92, 502–504 (2001)
M.M. Levine, Nat. Med. 9(1), 99–103 (2003)
W. Lin, M.L. Cormier, A. Samiee, A. Griffin, B. Johnson, C. Teng, G.E. Hardee, P.E Daddona, Pharm. Res. 18(12), 1789–1793 (2001)
W. Martanto, S.P. Davis, H.R. Holiday, J. Wang, H.S. Gill, M.R. Prausnitz, Pharm. Res. 21(6), 947–952 (2004)
J.A. Matriano, M. Cormier, J. Johnson, W.A. Young, M. Buttery, K. Nyam, P.E. Daddona, Pharm. Res. 19(1), 63–70 (2002)
D.V. McAllister, P.M. Wang, S.P. Davis, J. Park, P.J. Canatella, M.G. Allen, M.. Prausnitz, Proc. Natl. Acad. Sci. U. S. A. 100(24), 13755–13760 (2003)
J.A. Mikszta, J.B. Alarcon, J.M. Brittingham, D.E. Sutter, R.J. Pettis, N.G. Harvey, Nat. Med. 8(4), 415–419 (Apr 2002)
L. Nordquist, N. Roxhed, P. Griss, G. Stemme, Pharm. Res. 24(7), 1381–1388 (2007)
G.C. Paffenbarger, J. Am. Dent. Assoc. 84, 1333–1335 (1972)
J.-H. Park, M.G. Allen, M.R. Prausnitz, J. Control. Rel. 104(1), 51–66 (May 2005)
M.R. Prausnitz, Adv. Drug Deliv. Rev. 56, 581–587 (2004)
N. Roxhed, S. Rydholm, B. Samel, W. van der Wijngaart, P. Griss, G. Stemme, J. Micromechanics Microengineering 16(12), 2740–2746 (2006)
N. Roxhed, T.C. Gasser, P. Griss, G.A. Holzapfel, G. Stemme, IEEE ASME J. Microelectromech. Syst. (2007a) (in press)
N. Roxhed, B. Samel, L. Nordquist, P. Griss, G. Stemme, IEEE Trans. Biomed. Eng. (2007b) (in press)
J.T. Santini, A.C. Richards, R. Scheidt, M.J. Cima, R. Langer, Angew. Chem. Int. Ed. 39, 2396–2407 (2000)
C.F. Shaw, Metals and their compounds in the environment. (VCH, Weinheim, Germany, 1991), pp. 931–938
R.K. Sivamani, B. Stoeber, G.C. Wu, H. Zhai, D. Liepmann, H. Maibach, Skin Res. Technol. 11(11), 152–156 (2005)
B. Stoeber, D. Liepmann, IEEE ASME J. Microelectromech. Syst. 14(3), 472–479 (2005), ISSN 1057-7157
M.A.L. Teo, C. Shearwood, K.C. Ng, J. Lu, S. Moochhala, Biomedical Microdevices 7(1), 47–52 (2005), ISSN 1387-2176
B. Venugopal, T.D. Luckey, Metal toxicity in mammals, vol. 2. (Plenum Press, New York, 1978), p. 36
G. Voskerician, R.S. Shawgo, P.A. Hiltner, J.M. Anderson, M.J. Cima, R. Langer, IEEE Trans. Biomed. Eng. 51(4), 627–635 (2004), ISSN 0018-9294
U.I. Walther, S.C. Walther, B. Liebl, F.X. Reichl, K. Kehe, M. Nilius, R. Hickel, J. Biomed. Mater. Res. 63(5), 643–649 (2002)
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Roxhed, N., Griss, P. & Stemme, G. Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery. Biomed Microdevices 10, 271–279 (2008). https://doi.org/10.1007/s10544-007-9133-8
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DOI: https://doi.org/10.1007/s10544-007-9133-8