Abstract
Polymeric microneedles offer the advantages of being both mass-producible and inexpensive. However, their weakness lies in the fact that they are not adequate for sharp fabrication of a needle tip, which is an important factor for effective penetration. We hypothesized that effective penetration can be achieved using a high-velocity application system. Therefore, in the present study, we investigated the influence of various polymeric microneedle array geometries on skin permeability and irritation using such a system. Volar forearms of 16 healthy volunteers were treated using the microneedle system with four different parameters: applicator velocity (4.3, 6, and 8.5 m/s), tip radius (10, 15, and 20 μm), length (100, 200, and 300 μm), and number of needles (189 and 305 on a 50-mm2 area). A higher velocity of piercing clearly enhanced skin permeability and damage. A larger tip radius resulted in lower skin permeability and irritation at an applicator velocity of 4.3 m/s but did not have an effect at 6 m/s. Skin permeability was positively variable, ranging from 100 to 200 μm of needle length, and needle number showed no influence in the range investigated. In conclusion, a faster application speed could significantly enhance skin permeability and damage and compensate for insufficient penetration of the larger tip radius and shorter needles, which are also important factors for effective insertion.
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References
A. Arora, M.R. Prausnitz, S. Mitragotri, Micro-scale devices for transdermal drug delivery. Int. J. Pharm. 364(2), 227–236 (2008)
M.M. Badran, J. Kuntsche, A. Fahr, Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. Eur. J. Pharm. Sci. 36(4–5), 511–523 (2009)
S.M. Bal, J. Caussin, S. Pavel, J.A. Bouwstra, In vivo assessment of safety of microneedle arrays in human skin. Eur. J. Pharm. Sci. 35(3), 193–202 (2008)
S.P. Davis, B.J. Landis, Z.H. Adams, M.G. Allen, M.R. Prausnitz, Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J. Biomech. 37(8), 1155–1163 (2004)
R.F. Donnelly, D.I. Morrow, T.R. Singh, K. Migalska, P.A. McCarron, C. O’Mahony, A.D. Woolfson, Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev. Ind. Pharm. 35(10), 1242–1254 (2009)
A. Fullerton, T. Fischer, A. Lahti, K.P. Wilhelm, H. Takiwaki, J. Serup, Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 35(1), 1–10 (1996)
H.S. Gill, M.R. Prausnitz, Pocketed microneedles for drug delivery to the skin. J. Phys. Chem. Solids 69(5–6), 1537–1541 (2008)
Y.A. Gomaa, D.I. Morrow, M.J. Garland, R.F. Donnelly, L.K. El-Khordagui, V.M. Meidan, Effects of microneedle length, density, insertion time and multiple applications on human skin barrier function: assessments by transepidermal water loss. Toxicol. in Vitro. 24(7), 1971–1978 (2010)
S. Henry, D.V. McAllister, M.G. Allen, M.R. Prausnitz, Microfabricated microneedles: a novel approach to transdermal drug delivery. J. Pharm. Sci. 87(8), 922–925 (1998)
C.Y. Jin, M.H. Han, S.S. Lee, Y.H. Choi, Mass producible and biocompatible microneedle patch and functional verification of its usefulness for transdermal drug delivery. Biomed. Microdevices 11(6), 1195–1203 (2009)
S. Liu, M.N. Jin, Y.S. Quan, F. Kamiyama, H. Katsumi, T. Sakane, A. Yamamoto, The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J. Control. Release 161(3), 933–941 (2012)
W. Martanto, S.P. Davis, N.R. Holiday, J. Wang, H.S. Gill, M.R. Prausnitz, Transdermal delivery of insulin using microneedles in vivo. Pharm. Res. 21(6), 947–952 (2004)
W. Martanto, J.S. Moore, T. Couse, M.R. Prausnitz, Mechanism of fluid infusion during microneedle insertion and retraction. J. Control. Release 112(3), 357–361 (2006a)
W. Martanto, J.S. Moore, O. Kashlan, R. Kamath, P.M. Wang, J.M. O’Neal, M.R. Prausnitz, Microinfusion using hollow microneedles. Pharm. Res. 23(1), 104–113 (2006b)
K. Matsuo, S. Hirobe, Y. Yokota, Y. Ayabe, M. Seto, Y.S. Quan, F. Kamiyama, T. Tougan, T. Horii, Y. Mukai, N. Okada, S. Nakagawa, Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza. J. Control. Release 160(3), 495–501 (2012)
D.V. McAllister, M.G. Allen, M.R. Prausnitz, Microfabricated microneedles for gene and drug delivery. 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, Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc. Natl. Acad. Sci. U. S. A. 100(24), 13755–13760 (2003)
T. Miyano, Y. Tobinaga, T. Kanno, Y. Matsuzaki, H. Takeda, M. Wakui, K. Hanada, Sugar micro needles as transdermic drug delivery system. Biomed. Microdevices 7(3), 185–188 (2005)
J.H. Oh, H.H. Park, K.Y. Do, M. Han, D.H. Hyun, C.G. Kim, C.H. Kim, S.S. Lee, S.J. Hwang, S.C. Shin, C.W. Cho, Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein. Eur. J. Pharm. Biopharm. 69(3), 1040–1045 (2008)
J.H. Park, M.G. Allen, M.R. Prausnitz, Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Control. Release 104(1), 51–66 (2005)
J.H. Park, M.G. Allen, M.R. Prausnitz, Polymer microneedles for controlled-release drug delivery. Pharm. Res. 23(5), 1008–1019 (2006)
N. Roxhed, P. Griss, G. Stemme, Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery. Biomed. Microdevices 10(2), 271–279 (2008)
K. Sakaguchi, Y. Hirota, N. Hashimoto, W. Ogawa, T. Sato, S. Okada, K. Hagino, Y. Asakura, Y. Kikkawa, J. Kojima, Y. Maekawa, H. Nakajima, A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes. Diabetes Technol. Ther. 14(6), 485–491 (2012)
T. Sato, S. Okada, K. Hagino, Y. Asakura, Y. Kikkawa, J. Kojima, T. Watanabe, Y. Maekawa, K. Isobe, R. Koike, H. Nakajima, K. Asano, Measurement of glucose area under the curve using minimally invasive interstitial fluid extraction technology: evaluation of glucose monitoring concepts without blood sampling. Diabetes Technol. Ther. 13(12), 1194–1200 (2011)
A.L. Teo, C. Shearwood, K.C. Ng, J. Lu, S. Moochhal, Transdermal microneedles for drug delivery applications. Mater. Sci. Eng. B 132, 151–154 (2006)
F.J. Verbaan, S.M. Bal, D.J. van den Berg, W.H. Groenink, H. Verpoorten, R. Lüttge, J.A. Bouwstra, Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. J. Control. Release 117(2), 238–245 (2007)
F.J. Verbaan, S.M. Bal, D.J. van den Berg, J.A. Dijksman, M. van Hecke, H. Verpoorten, A. van den Berg, R. Luttge, J.A. Bouwstra, Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method. J. Control. Release 128(1), 80–88 (2008)
Y. Xie, B. Xu, Y. Gao, Controlled transdermal delivery of model drug compounds by MEMS microneedle array. Nanomedicine 1(2), 184–190 (2005)
G. Yan, K.S. Warner, J. Zhang, S. Sharma, B.K. Gale, Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. Int. J. Pharm. 391(1–2), 7–12 (2010)
M. Yang, J.D. Zahn, Microneedle insertion force reduction using vibratory actuation. Biomed. Microdevices 6(3), 177–182 (2004)
Acknowledgments
We thank M. Takahashi and S. Hosoya (Sysmex Corporation, Japan) for their experimental assistance. We also thank Y. Sasagawa and K. Ishii (Sysmex Corporation, Japan) for their statistical advices.
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All authors are employees of Sysmex.
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Watanabe, T., Hagino, K. & Sato, T. Evaluation of the effect of polymeric microneedle arrays of varying geometries in combination with a high-velocity applicator on skin permeability and irritation. Biomed Microdevices 16, 591–597 (2014). https://doi.org/10.1007/s10544-014-9861-5
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DOI: https://doi.org/10.1007/s10544-014-9861-5