Pharmaceutical Research

, Volume 28, Issue 1, pp 41–57 | Cite as

Design, Optimization and Characterisation of Polymeric Microneedle Arrays Prepared by a Novel Laser-Based Micromoulding Technique

  • Ryan F. Donnelly
  • Rita Majithiya
  • Thakur Raghu Raj Singh
  • Desmond I. J. Morrow
  • Martin J. Garland
  • Yusuf K. Demir
  • Katarzyna Migalska
  • Elizabeth Ryan
  • David Gillen
  • Christopher J. Scott
  • A. David Woolfson
Research Paper



Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.


A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.


Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 μm and 900 μm in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 μm microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 μm Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted.


In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles.


laser engineering microneedles optical coherence tomography transdermal drug delivery 



This work was supported by BBSRC grant number BB/E020534/1 and Invest Northern Ireland Proof of Concept grant number POC21A. The authors thank Dr. Daniel Woods for his assistance with OCT and Michelson Diagnostics (Kent, England) for the use of their OCT imaging equipment.


  1. 1.
    Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87:922–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Prausnitz MR. Microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56:581–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Davis SP, Martanto W, Allen MG, Prausnitz MR. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans Biomed Eng. 2005;52:909–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Moon SJ, Lee SS, Lee HS, Kwon TH. Fabrication of microneedle array using LIGA and hot embossing process. Microsyst Technol Micro Nanosyst Informat Storage Proc Syst. 2005;11:311–8.Google Scholar
  5. 5.
    Park JH, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release. 2005;104:51–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Stoeber B, Liepmann D. Arrays of hollow out-of-plane microneedles for drug delivery. J Microelectromech Syst. 2005;14:472–9.CrossRefGoogle Scholar
  7. 7.
    Trichur R, Kim S, Zhu X, Suk JW, Hong C-C, Choi J-W, et al. Development of plastic microneedles for transdermal interfacing using injection molding techniques. Micro Total Analysis System. 2002;1:395–7.Google Scholar
  8. 8.
    Yang M, Zahn JD. Microneedle insertion force reduction using vibratory actuation. Biomed Microdevices. 2004;6:177–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Donnelly RF, Morrow DIJ, McCarron PA, Woolfson AD, Morrissey A, Juzenas P, et al. Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: potential for enhanced topical photodynamic therapy. J Control Release. 2008;129:154–62.CrossRefPubMedGoogle Scholar
  10. 10.
    Mikszta JA, Dekker JP, Harvey NG, Dean CH, Brittingham JM. Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. Infect Immun. 2006;74:6806–10.CrossRefPubMedGoogle Scholar
  11. 11.
    Coulman SA, Barrow D, Anstey A, Gateley C, Morrissey A, Wilke N. Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Curr Drug Deliv. 2006;3:65–75.CrossRefPubMedGoogle Scholar
  12. 12.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A. 2003;100:13755–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117:227–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang DD. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release. 2004;97:503–11.PubMedGoogle Scholar
  15. 15.
    Ito Y, Jun-Ichiro Y, Keiji S, Nobuyuki S, Kanji T. Self-dissolving microneedles for the percutaneous absorption of EPO in mice. J Drug Target. 2006;14:255–61.CrossRefPubMedGoogle Scholar
  16. 16.
    Donnelly RF, Morrow DIJ, McCarron PA, Woolfson AD, Morrissey A, Juzenas P, et al. Microneedle arrays permit true intradermal delivery of a preformed photosensitiser. Photochem Photobiol. 2009;85:195–204.CrossRefPubMedGoogle Scholar
  17. 17.
    Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine. 2006;24:1653–64.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang PM, Cornwell M, Hill J, Prausnitz MR. Precise microinjection into skin using hollow microneedles. J Invest Dermatol. 2006;126:1080–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Ito Y, Eiji H, Atsushi S, Nobuyuki S, Kanji T. Feasibility of microneedles for percutaneous absorption of insulin. Eur J Pharm Sci. 2006;29:82–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Kaushik S, Allen HH, Donald DD, McAllister DV, Smitra S, Allen MG, et al. Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001;92:502–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Donnelly RF, Thakur RRS, Tunney MM, Morrow DIJ, McCarron PA, O’Mahony C, et al. Movement of microorganisms through microneedle-induced holes is possible, but initiation of infection is unlikely. Pharm Res. 2009;26:2513–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Banga AK. Microporation applications for enhancing drug delivery. Expert Opin Drug Deliv. 2009;6:343–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Martanto W, Davis SP, Nicholas RH, Wang J, Gill HS, Prausnitz MR. Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004;21:947–52.CrossRefPubMedGoogle Scholar
  24. 24.
    Park JH, Allen MG, Prausnitz MR. Polymer microneedles for controlled-release drug delivery. Pharm Res. 2006;23:1008–19.CrossRefPubMedGoogle Scholar
  25. 25.
    Donnelly RF, Morrow DIJ, Thakur RRS, Migalska K, McCarron PA, O’Mahony C, et al. Processing difficulties and instability of carbohydrate microneedle arrays. Drug Devel Ind Pharm. 2009;35:1242–54.CrossRefGoogle Scholar
  26. 26.
    Kalluri H, Banga A. Kinetics of pore closure in microneedle treated skin. CRS Denmark, July 2009.Google Scholar
  27. 27.
    Arora A, Prausnitz M, Mitragotri S. Micro-scale devices for transdermal drug delivery. Int J Pharm. 2008;364:227–36.CrossRefPubMedGoogle Scholar
  28. 28.
    Lee JW, Park JH, Prausnitz MR. Dissolving microneedles for transdermal drug delivery. Biomaterials. 2008;29:2113–24.CrossRefPubMedGoogle Scholar
  29. 29.
    Woolfson AD, McCafferty DF, McCallion CR, McAdams ET, Anderson J McC. Moisture-activated, electrically conducting bioadhesive hydrogels as interfaces for bioelectrodes: effect of film hydration on cutaneous adherence in wet environments. J Appl Polym Sci. 1995;58:1291–6.CrossRefGoogle Scholar
  30. 30.
    Fourtanier A, Berrebi C. Miniature pig as an animal model to study photoaging. Photochem Photobiol. 1989;50:771–84.CrossRefPubMedGoogle Scholar
  31. 31.
    Colea L, Heard C. Skin permeation enhancement potential of Aloe Vera and a proposed mechanism of action based upon size exclusion and pull effect. Int J Pharm. 2007;333:10–6.CrossRefGoogle Scholar
  32. 32.
    Nirogi RVS, Kandikere VN, Shukla M, Mudigonda K, Ajjala DR. A simple and rapid HPLC/UV method for the simultaneous quantification of theophylline and etofylline in human plasma. J Chromatogr B. 2007;848:271–6.CrossRefGoogle Scholar
  33. 33.
    Girish V, Vijayalakshmi A. Affordable image analysis using NIH Image/ImageJ. Ind J Cancer. 2004;41:47.Google Scholar
  34. 34.
    Aoyagi S, Hayato I, Yuichi I, Mitsuo F, Ogawa H. Laser fabrication of high aspect ratio thin holes on biodegradable polymer and its application to a microneedle. Sens Actuators A Phys. 2007;139:293–302.CrossRefGoogle Scholar
  35. 35.
    Han M, Hyun DH, Park HH, Lee SS, Kim CH, Kim CG. A novel fabrication process for out-of-plane microneedle sheets of biocompatible polymer. J Micromechanics Microengineering. 2007;17:1184–91.CrossRefGoogle Scholar
  36. 36.
    Ovsianikov A, Chichkov B, Mente P, Monteiro-riviere NA, Doraiswamy A, Narayan RJ. Two photon polymerization of polymer-ceramic hybrid materials for transdermal drug delivery. Int J Appl Ceramic Technol. 2007;4:22–9.CrossRefGoogle Scholar
  37. 37.
    Perennes F, Marmiroli B, Matteucci M, Tormen M, Vaccari L, Fabrizio ED. Sharp beveled tip hollow microneedle arrays fabricated by LIGA and 3D soft lithography with polyvinyl alcohol. J Micromechanics Microengineering. 2006;16:473–9.CrossRefGoogle Scholar
  38. 38.
    Sammoura F, Kang JJ, Heo YM, Tae SJ, Liwei L. Polymeric microneedle fabrication using a microinjection molding technique. Microsyst Technol. 2007;13:517–22.CrossRefGoogle Scholar
  39. 39.
    Sullivan SP, Murthy N, Prausnitz MR. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv Mater. 2008;20:933–8.CrossRefGoogle Scholar
  40. 40.
    Lippmann JM, Geiger EJ, Albert AP. Polymer investment molding: method for fabricating hollow, microscale parts. Sens Actuators A Phys. 2007;134:2–10.CrossRefGoogle Scholar
  41. 41.
    Madou MJ. Fundamentals of microfabrication. 2nd ed. Boca Raton: CRC Press; 1997. p. 1–71.Google Scholar
  42. 42.
    Landa G, Rosen RB, Garcia PMT, Seiple WH. Combined three-dimensional spectral OCT/SLO topography and microperimetry: Steps toward achieving functional spectral OCT/SLO. Ophthalmic Res. 2009;43:92–8.CrossRefPubMedGoogle Scholar
  43. 43.
    König K, Speicher M, Bückle R, Reckfort J, McKenzie G, Welzel J, et al. Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases. J Biophoton. 2009;2:389–97.CrossRefGoogle Scholar
  44. 44.
    Haq MI, Smith E, John DN, Kalavala M, Edwards C, Anstey A, et al. Clinical administration of microneedles: skin puncture, pain and sensation. Biomed Microdev. 2009;11:35–47.CrossRefGoogle Scholar
  45. 45.
    Pearton M, Allender C, Brain K, Anstey A, Gateley C, Wilke N, et al. Gene delivery to the epidermal cells of human skin explants using microfabricated microneedles and hydrogel formulations. Pharm Res. 2007;25:407–16.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ryan F. Donnelly
    • 1
  • Rita Majithiya
    • 1
  • Thakur Raghu Raj Singh
    • 1
  • Desmond I. J. Morrow
    • 1
  • Martin J. Garland
    • 1
  • Yusuf K. Demir
    • 1
  • Katarzyna Migalska
    • 1
  • Elizabeth Ryan
    • 1
  • David Gillen
    • 2
  • Christopher J. Scott
    • 1
  • A. David Woolfson
    • 1
  1. 1.School of PharmacyQueen’s University Belfast Medical Biology CentreBelfastUK
  2. 2.Blue Acre TechnologyDundalkIreland

Personalised recommendations