Abstract
There is a significant interest in the application of microneedles in intradermal drug delivery systems. Previous studies have demonstrated that skin permeation of drugs can be increased by orders of magnitude with microneedle insertion. In this study, emphasis is placed on the development of low cost, painless intradermal microneedle systems that can enhance the percutaneous drug permeation. Microneedles of octagonal pyramidal shape with the length of 150 μm were employed, and the capabilities of skin permeation enhancement under different delivery conditions were examined. The delivery parameters taken into account included the insertion time and the area of insertion. It was found that when solid microneedle arrays of 150 μm in length were pierced into human dermatomed skin for 5 to 60 s, microconduits with the depth of 50 to 80 μm were created to facilitate the percutaneous permeation of drugs. In percutaneous tests, it was demonstrated that the permeability coefficient of calcein (MW = 622.55) was significantly increased by 104 to 105 times compared to that on intact skin. In terms of biocompatibility, biological evaluation indicated a broad spectrum of safety for the microneedle system. These results suggest that the octagonal pyramidal microneedles can be an effective tool in developing novel intradermal drug delivery system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
P. Aggarwal, C. R. Johnston, Sens. Actuators B 102, 226–234 (2004)
F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, J. Birchall, Br. J. Dermatol. 150, 869–877 (2004)
H. S. Gill, D. Denson and M. R. Prausnitz, The Preliminary Program for AIChE 2006 Annual Meeting (San Francisco, USA, 2006)
I. Haider, R. J. Pettis, N. Davison, C. Richard and D. Jeffrey, Proceedings from the 25th Annual Meeting of the American Society of Biomechanics (San Diego, CA, 2001)
S. Henry, D. V. McAllister, M. G. Allen, M. R. Prausnitz, J. Pharm. Sci. 87, 922–925 (1998)
Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, D.C., 1996)
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)
G. Kotzar, M. Freas, P. Abel, A. Fleischman, S. Roy, C. Zorman, J. M. Moran, J. Melzak, Biomaterials 23, 2737–2750 (2002)
W. Martanto, S. P. Davis, N. R. Holiday, J. Wang, H. S. Gill, M. R. Prausnitz, Pharm. Res. 21, 947–952 (2004)
W. Martanto, J. S. Moore, T. Couse, M. R. Prausnitz, J. Control. Release 112, 351–361 (2006)
D. V. McAllister, M. G. Allen, M. R. Prausnitz, Ann. Rev. Biomed. Eng. 2, 289–313 (2000)
J. A. Mikszta, J. B. Alarcon, J. M. Brittingham, D. E. Sutter, R. J. Pettis, N. G. Harvey, Nat. Med. 8, 415–419 (2002)
S. Mitragotri, J. Kost, Adv. Drug Deliv. Rev. 56, 589–601 (2004)
A. Morrissey, N. Wilke, C. Hilbert and J. O’Brien, 10th International Conference on Electroanalysis, ESEAC04 (Galway, Ireland, 2004)
A. Morrissey, N. Wilke, S. A. Coulman, M. Pearton, A. Anstey, C. Gateley, C. Allender, K. Brain and J. C. Birchall, The 3rd European Medical and Biological Engineering Conference (Prague, Czech Republic, 2005)
Organization for Economic Cooperation and Development (OECD), OECD Guidelines for testing of chemicals, No. 428: Skin Absorption: In vitro Method (OECD, 2004)
M. R. Prausnitz, Adv. Drug Deliv. Rev. 35, 61–76 (1999)
M. R. Prausnitz, Adv. Drug Deliv. Rev. 56, 581–587 (2004)
M. R. Prausnitz, S. Mitragotri, R. Langer, Nat. Rev. Drug Discov. 3, 115–124 (2004)
M. L. Reed, W-K. Lye, Proceedings of the IEEE 92, 56–75 (2004)
H. Sasaki, M. Shikida, K. Sato, IEEJ Trans 2, 340–347 (2007)
A. L. Teo, C. Shearwood, K. C. Ng, J. Lu, S. Moochhala, Mat. Sci. Eng. B 132, 151–154 (2006)
F. J. Verbaan, S. M. Bal, D. J. van den Berg, W. H. H. Groenink, H. Verpoorten, R. Lüttge, J. A. Bouwstra, J. Control. Release 117, 238–245 (2007)
A. C. Williams, B. W. Barry, Adv. Drug Deliv. Rev. 56, 603–618 (2004)
N. Wilke, A. Morrissey, S. Ye and J. O’Brien, EMN04 (Paris, France, 2004), p20–21
N. Wilke, A. Mulcahy, S.-R. Ye, A. Morrissey, Microelectron. J. 36, 650–656 (2005)
N. Wilke, M. L. Reed, A. Morrissey, J. Micromechanics Microengineering 16, 808–814 (2006)
N. Wilke, A. Morrissey, J. Micromechanics Microengineering 17, 238–244 (2007)
Y. Xie, B. Xu, Y. Gao, Nanomedicine: NBM 1, 184–190 (2005)
B. Xu and Y. Gao, Chinese patent, CN 200310122500 (2003)
Acknowledgements
We would like to thank Prof. Weidong Hao and his group in the Department of Toxicology of School of Public Health, Peking University, for their support in the biocompatibility evaluation of microneedle arrays; Cheng Zhan (National Institute of Biological Sciences, Peking, China) for Confocal Laser Scanning Microscope (CLSM) imaging of skin samples; the Department of Pathology, Peking University, for their support of frozen tissue sections. The work was partly supported by the Important Direction Program, Chinese Academy of Sciences (No. kjcx2-sw-h12–01).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wu, Y., Qiu, Y., Zhang, S. et al. Microneedle-based drug delivery: studies on delivery parameters and biocompatibility. Biomed Microdevices 10, 601–610 (2008). https://doi.org/10.1007/s10544-008-9171-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-008-9171-x