Skip to main content
SpringerLink
Log in

Vaccine Delivery Using Microneedles

  • Chapter
  • First Online:
Molecular Vaccines

Abstract

Breaching the skin’s stratum corneum barrier raises the possibility of administration of vaccines, gene vectors, antibodies, photosensitisers and even nanoparticles, all of which have at least their initial effect on populations of skin cells. Intradermal vaccine delivery, in particular, holds enormous potential for improved therapeutic outcomes for patients, particularly those in the developing world. Various microneedle-based vaccine delivery strategies have been employed, and here we discuss each one in turn. We also describe the importance of cutaneous immunobiology on the effect produced by microneedle-mediated intradermal vaccination.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hegde, N.R., Kaveri, S.V., Bayry, J.: Recent advances in the administration of vaccines for infectious diseases: microneedles as painless delivery devices for mass vaccination. Drug Discov Today 16, 1061–1068 (2011)

    PubMed  Google Scholar 

  2. Koutsonanos, D., del Pilar Martin, M., Zarnitsyn, V., Sullivan, S., Compans, R., Skountzou, I., et al.: Transdermal influenza immunization with vaccine-coated microneedle arrays. PLoS One 4, e4773 (2009)

    PubMed  Google Scholar 

  3. Nicolas, J., Guy, B.: Intradermal, epidermal and transcutaneous vaccination: from immunology to clinical practice. Expert Rev Vaccines 7, 1201–1214 (2008)

    PubMed  Google Scholar 

  4. Warger, T., Schild, H., Rechtsteiner, G.: Initiation of adaptive immune responses by transcutaneous immunization. Immunol Lett 109, 13–20 (2007)

    PubMed  CAS  Google Scholar 

  5. Stoitzner, P., Sparber, F., Tripp, C.H.: Langerhans cells as targets for immunotherapy against skin cancer. Immunol Cell Biol 88, 431–437 (2010)

    PubMed  Google Scholar 

  6. Kenney, R.T., Yu, J., Guebre-Xabier, M., Frech, S.A., Lambert, A., Heller, B.A., et al.: Induction of protective immunity against lethal anthrax challenge with a patch. J Infect Dis 190, 774–782 (2004)

    PubMed  Google Scholar 

  7. Combadiere, B., Vogt, A., Mahe, B., Costagliola, D., Hadam, S.: Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One 5, e10818 (2010)

    PubMed  Google Scholar 

  8. Lambert, P.H., Laurent, P.E.: Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine 26, 3197–3208 (2008)

    PubMed  CAS  Google Scholar 

  9. Wysocki, A.B.: Skin anatomy, physiology, and pathophysiology. Nurs Clin North Am 34, 777–797 (1999)

    PubMed  CAS  Google Scholar 

  10. Chuong, C.M., Nickoloff, B.J., Elias, P.M., Goldsmith, L.A., Macher, E., Maderson, P.A., et al.: What is the ‘true’ function of skin? Exp Dermatol 11, 159–187 (2002)

    PubMed  CAS  Google Scholar 

  11. Williams, A.C., Barry, B., Barry, B.W.: Skin absorption enhancers. Crit Rev Ther Drug Carrier Syst 9, 305–353 (1992)

    PubMed  CAS  Google Scholar 

  12. Wiechers, J.W.: The barrier function of the skin in relation to percutaneous absorption of drugs. Pharmaceutisch weekblad Scientific 11, 185–198 (1989)

    CAS  Google Scholar 

  13. Tobin, D.: Biochemistry of human skin–our brain on the outside. Chem Soc Rev 35, 52–67 (2006)

    PubMed  CAS  Google Scholar 

  14. Asbill, C.S., El Kattan, A.F., Michniak, B.: Enhancement of transdermal drug delivery: chemical and physical approaches. Crit Rev Ther Drug Carrier Syst 17, 621–658 (2000)

    PubMed  CAS  Google Scholar 

  15. Menon, G.: New insights into skin structure: scratching the surface. Adv Drug Deliv Rev 54, S3–S17 (2002)

    PubMed  CAS  Google Scholar 

  16. Siddiqui, O.: Physicochemical, physiological, and mathematical considerations in optimizing percutaneous absorption of drugs. Crit Rev Ther Drug Carrier Syst 6, 1–38 (1989)

    PubMed  CAS  Google Scholar 

  17. Scheuplein, R.J.: Permeability of the skin: a review of major concepts. Curr Probl Dermatol 7, 172–186 (1978)

    PubMed  CAS  Google Scholar 

  18. Steinman, R.M., Hawiger, D., Nussenzweig, M.C.: Tolerogenic dendritic cells. Annu Rev Immunol 21, 685–711 (2003)

    PubMed  CAS  Google Scholar 

  19. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y.J., et al.: Immunobiology of dendritic cells. Annu Rev Immunol 18, 767–811 (2000)

    PubMed  CAS  Google Scholar 

  20. Kleijwegt, F.S., Jansen, D.T., Teeler, J., Joosten, A.M., Laban, S., Nikolic, T., Roep, B.O.: Tolerogenic dendritic cells impede priming of naïve CD8(+) T cells and deplete memory CD8(+) T cells. Eur J Immunol 43(1), 85–92 (2012). doi:10.1002/eji.201242879

    PubMed  Google Scholar 

  21. Ginhoux, F., Ng, L.G., Merad, M.: Understanding the murine cutaneous dendritic cell network to improve intradermal vaccination strategies. Curr Top Microbiol Immunol 351, 1–24 (2012)

    PubMed  CAS  Google Scholar 

  22. Teunissen, M.B., Haniffa, M., Collin, M.P.: Insight into the immunobiology of human skin and functional specialization of skin dendritic cell subsets to innovate intradermal vaccination design. Curr Top Microbiol Immunol 351, 25–76 (2012)

    PubMed  CAS  Google Scholar 

  23. Steinman, R.M., Hemmi, H.: Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol 311, 17–58 (2006)

    PubMed  CAS  Google Scholar 

  24. Merad, M., Ginhoux, F., Collin, M.: Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol 8, 935–947 (2008)

    PubMed  CAS  Google Scholar 

  25. Romani, N., Clausen, B.E., Stoitzner, P.: Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev 234, 120–141 (2010)

    PubMed  CAS  Google Scholar 

  26. Takahara, K., Omatsu, Y., Yashima, Y., Maeda, Y., Tanaka, S., Iyoda, T., et al.: Identification and expression of mouse Langerin (CD207) in dendritic cells. Int Immunol 14, 433–444 (2002)

    PubMed  CAS  Google Scholar 

  27. Valladeau, J., Saeland, S.: Cutaneous dendritic cells. Semin Immunol 17, 273–283 (2005)

    PubMed  CAS  Google Scholar 

  28. Steinman, R.M., Nussenzweig, M.C.: Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. U. S. A. 99, 351–358 (2002)

    PubMed  CAS  Google Scholar 

  29. Larregina, A.T., Falo Jr., L.D.: Changing paradigms in cutaneous immunology: adapting with dendritic cells. J Invest Dermatol 124, 1–12 (2005)

    PubMed  CAS  Google Scholar 

  30. Bursch, L.S., Wang, L., Igyarto, B., Kissenpfennig, A., Malissen, B., Kaplan, D.H., et al.: Identification of a novel population of Langerin + dendritic cells. J Exp Med 204, 3147–3156 (2007)

    PubMed  CAS  Google Scholar 

  31. Ginhoux, F., Collin, M.P., Bogunovic, M., Abel, M., Leboeuf, M., Helft, J., et al.: Blood-derived dermal langerin + dendritic cells survey the skin in the steady state. J Exp Med 204, 3133–3146 (2007)

    PubMed  CAS  Google Scholar 

  32. Poulin, L.F., Henri, S., de Bovis, B., Devilard, E., Kissenpfennig, A., Malissen, B.: The dermis contains langerin + dendritic cells that develop and function independently of epidermal Langerhans cells. J Exp Med 204, 3119–3131 (2007)

    PubMed  CAS  Google Scholar 

  33. Romani, N., Koide, S., Crowley, M., Witmer-Pack, M., Livingstone, A.M., Fathman, C.G., et al.: Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med 169, 1169–1178 (1989)

    PubMed  CAS  Google Scholar 

  34. Stoitzner, P., Tripp, C.H., Eberhart, A., Price, K.M., Jung, J.Y., Bursch, L., et al.: Langerhans cells cross-present antigen derived from skin. Proc. Natl. Acad. Sci. U. S. A. 103, 7783–7788 (2006)

    PubMed  CAS  Google Scholar 

  35. Stoitzner, P., Green, L.K., Jung, J.Y., Price, K.M., Tripp, C.H., Malissen, B., et al.: Tumor immunotherapy by epicutaneous immunization requires langerhans cells. J Immunol 180, 1991–1998 (2008)

    PubMed  CAS  Google Scholar 

  36. Cunningham, A.L., Carbone, F., Geijtenbeek, T.B.: Langerhans cells and viral immunity. Eur J Immunol 38, 2377–2385 (2008)

    PubMed  CAS  Google Scholar 

  37. Kautz-Neu, K., Meyer, R.G., Clausen, B.E., von Stebut, E.: Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. Exp Dermatol 19, 760–771 (2010)

    PubMed  CAS  Google Scholar 

  38. Bennett, C.L., van Rijn, E., Jung, S., Inaba, K., Steinman, R.M., Kapsenberg, M.L., et al.: Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J Cell Biol 169, 569–576 (2005)

    PubMed  CAS  Google Scholar 

  39. Stoecklinger, A., Eticha, T.D., Mesdaghi, M., Kissenpfennig, A., Malissen, B., Thalhamer, J., et al.: Langerin + dermal dendritic cells are critical for CD8+ T cell activation and IgH gamma-1 class switching in response to gene gun vaccines. J Immunol 186, 1377–1383 (2011)

    PubMed  CAS  Google Scholar 

  40. Angel, C.E., Lala, A., Chen, C.J., Edgar, S.G., Ostrovsky, L.L., Dunbar, P.R.: CD14+ antigen-presenting cells in human dermis are less mature than their CD1a + counterparts. Int Immunol 19, 1271–1279 (2007)

    PubMed  CAS  Google Scholar 

  41. Angel, C.E., Chen, C.J., Horlacher, O.C., Winkler, S., John, T., Browning, J., et al.: Distinctive localization of antigen-presenting cells in human lymph nodes. Blood 113, 1257–1267 (2009)

    PubMed  CAS  Google Scholar 

  42. Klechevsky, E., Morita, R., Liu, M., Cao, Y., Coquery, S., Thompson-Snipes, L., et al.: Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells. Immunity 29, 497–510 (2009)

    Google Scholar 

  43. van der Aar, A.M., de Groot, R., Sanchez-Hernandez, M., Taanman, E.W., van Lier, R.A., Teunissen, M.B., et al.: Cutting edge: virus selectively primes human langerhans cells for CD70 expression promoting CD8+ T cell responses. J Immunol 187, 3488–3492 (2011)

    PubMed  Google Scholar 

  44. Garland, M., Migalska, K., Mahmood, T.M.T., Singh, T.R.R., Woolfson, A.D., Donnelly, R.: Microneedle arrays as medical devices for enhanced transdermal drug delivery. Expert Rev Med Devices 8, 459–482 (2011)

    PubMed  CAS  Google Scholar 

  45. Donnelly, R., Majithiya, R., Singh, T., Morrow, D., Garland, M., Demir, Y.: Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique. Pharm Res 28, 41–57 (2011)

    PubMed  CAS  Google Scholar 

  46. Chen, X., Fernando, G.J.P., Crichton, M., Flaim, C., Yukiko, S., Corbett, H.J., et al.: Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization. J Controlled Release. 152, 349–355 (2011)

    CAS  Google Scholar 

  47. Henry, S., McAllister, D.V., Allen, M.G., Prausnitz, M.R.: Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 87, 922–925 (1998)

    PubMed  CAS  Google Scholar 

  48. Prausnitz, M., Mikszta, J., Cormier, M., Andrianov, A.: Microneedle-based vaccines. Curr Top Microbiol Immunol 333, 369–393 (2009)

    PubMed  CAS  Google Scholar 

  49. Donnelly, R., Raj Singh, T.R., Woolfson, A.D.: Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv 17, 187–207 (2010)

    PubMed  CAS  Google Scholar 

  50. Zhou, C., Liu, Y., Wang, H., Zhang, P., Zhang, J.: Transdermal delivery of insulin using microneedle rollers in vivo. Int J Pharm 392, 127–133 (2010)

    PubMed  CAS  Google Scholar 

  51. Ding, Z., Verbaan, F.J., Bivas- Benita, M., Bungener, L., Huckriede, A., Kersten, G., et al.: Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice. J Controlled Release. 136, 71–78 (2009)

    CAS  Google Scholar 

  52. Ding, Z., Van Riet, E., Romeijn, S., Kersten, G.F.A., Jiskoot, W., Bouwstra, J.A.: Immune modulation by adjuvants combined with diphtheria toxoid administered topically in BALB/c mice after microneedle array pretreatment. Pharm Res 26, 1635–1643 (2009)

    PubMed  CAS  Google Scholar 

  53. Bal, S.M., Slütter, B., van Riet, E., Kruithof, A.C., Ding, Z., Kersten, G.F.A., et al.: Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations. J Controlled Release. 142, 374–383 (2010)

    CAS  Google Scholar 

  54. Bhowmik, T., D’Souza, B., Shashidharamurthy, R., Oettinger, C., Selvaraj, P., D’Souza, M.: A novel microparticulate vaccine for melanoma cancer using transdermal delivery. J Microencapsul 28, 294–300 (2011)

    PubMed  CAS  Google Scholar 

  55. Cleary, G.: Microneedles for drug delivery. Pharm Res 28, 1–6 (2011)

    PubMed  CAS  Google Scholar 

  56. Shah, U.U., Roberts, M., Orlu Gul, M., Tuleu, C., Beresford, M.W.: Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs). Int J Pharm 416, 1–11 (2011)

    PubMed  CAS  Google Scholar 

  57. Kim, Y., Quan, F., Compans, R.W., Kang, S., Prausnitz, M.R.: Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J Controlled Release. 142, 187–195 (2010)

    CAS  Google Scholar 

  58. Hiraishi, Y., Nandakumar, S., Choi, S., Lee, J., Kim, Y., Prausnitz, M.R., et al.: Bacillus Calmette-Guérin vaccination using a microneedle patch. Vaccine 29, 2626–2636 (2011)

    PubMed  CAS  Google Scholar 

  59. Weldon, W., Martin, M., Zarnitsyn, V., Wang, B., Koutsonanos, D., Skountzou, I.: Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity. Clinical and vaccine immunol. 18, 647–654 (2011)

    CAS  Google Scholar 

  60. Prow, T.: Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice. Small 6, 1776–1784 (2010)

    PubMed  CAS  Google Scholar 

  61. Corbett, H., Chen, X., Frazer, I.: Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model. PLoS One 5, e13460 (2010)

    PubMed  Google Scholar 

  62. Fernando, G.J.P., Chen, X., Prow, T., Crichton, M., Fairmaid, E.: Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model. PLoS One 5, e10266 (2010)

    PubMed  Google Scholar 

  63. Matriano, J., Cormier, M., Johnson, J., Young, W., Buttery, M., Cormier, M., et al.: Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization. Pharm Res 19, 63–70 (2002)

    PubMed  CAS  Google Scholar 

  64. Widera, G., Johnson, J., Kim, L., Libiran, L., Nyam, K., Daddona, P.E., et al.: Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine 24, 1653–1664 (2006)

    PubMed  CAS  Google Scholar 

  65. Escobar-Chvez, J., Bonilla- Martinez, D., Villegas-González, M.A., Molina Trinidad, E., Casas Alancaster, N., et al.: Microneedles: a valuable physical enhancer to increase transdermal drug delivery. J Clin Pharmacol 51, 964–977 (2011)

    Google Scholar 

  66. Amorij, J., Frijlink, H., Wilschut, J., Huckriede, A.: Needle-free influenza vaccination. Lancet Infect Dis 10, 699–711 (2010)

    PubMed  Google Scholar 

  67. Wang, P., Cornwell, M., Hill, J., Prausnitz, M.: Precise microinjection into skin using hollow microneedles. J Invest Dermatol 126, 1080–1087 (2006)

    PubMed  CAS  Google Scholar 

  68. Frost, G.I.: Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv 4, 427–440 (2007)

    PubMed  CAS  Google Scholar 

  69. Bal, S., Ding, Z., van Riet, E., Jiskoot, W., Bouwstra, J.: Advances in transcutaneous vaccine delivery: Do all ways lead to Rome? J Controlled Release. 148, 266–282 (2010)

    CAS  Google Scholar 

  70. Van Damme, P., Oosterhuis-Kafeja, F., Van der Wielen, M., Almagor, Y., Sharon, O., Levin, Y.: Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 27, 454–459 (2009)

    PubMed  Google Scholar 

  71. Alarcon, J., Hartley, A., Harvey, N., Mikszta, J.: Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines. Clin Vaccine Immunol 14, 375–381 (2007)

    PubMed  CAS  Google Scholar 

  72. Mikszta, J., Dekker, J., Harvey, N., Dean, C., Brittingham, J., Huang, J., et al.: Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. Infect Immun 74, 6806–6810 (2006)

    PubMed  CAS  Google Scholar 

  73. Sullivan, S., Koutsonanos, D., Del Pilar Martin, M., Lee, J., Zarnitsyn, V., Compans, R.W., et al.: Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16, 915–920 (2010)

    PubMed  CAS  Google Scholar 

  74. Raphael, A., Prow, T., Crichton, M., Chen, X., Fernando, G.J.P., Prow, T.: Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays. Small 6, 1785–1793 (2010)

    PubMed  CAS  Google Scholar 

  75. Chabri, F., Bouris, K., Jones, T., Barrow, D., Hann, A., Allender, C., et al.: Microfabricated silicon microneedles for nonviral cutaneous gene delivery. Br J Dermatol 150, 869–877 (2004)

    PubMed  CAS  Google Scholar 

  76. Prow, T.W., Chen, X., Prow, N.A., Fernando, G.J., Tan, C.S., Raphael, A.P., et al.: Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice. Small 16, 1776–1784 (2010)

    Google Scholar 

  77. Birchall, J., Coulman, S., Pearton, M., Allender, C., Brain, K., Coulman, S., et al.: Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch micro-fabricated micro-needles. J Drug Target 13, 415–421 (2005)

    PubMed  CAS  Google Scholar 

  78. Coulman, S.A., Barrow, D., Anstey, A., Gateley, C., Morrissey, A., Wilke, N., et al.: Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Curr Drug Deliv 3, 65–75 (2006)

    PubMed  CAS  Google Scholar 

  79. 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 25, 407–416 (2008)

    PubMed  CAS  Google Scholar 

  80. Gill, H.S., Soderholm, J., Prausnitz, M.R., Sallberg, M., Sderholm, J., Sllberg, M.: Cutaneous vaccination using microneedles coated with hepatitis C DNA vaccine. Gene Ther 17, 811–814 (2010)

    PubMed  CAS  Google Scholar 

  81. Choi, S. O., Park, J. H., Gill, H. S., Choi, Y., Allen, M.G., M. R.: Prausnitz. Microneedles electrode array for electroporation of skin for gene therapy. Controlled Release Society 32nd Annual Meeting & Exposition Transactions. 318 (2005)

    Google Scholar 

  82. Hooper, J., Golden, J., Ferro, A., King, A.: Smallpox DNA vaccine delivered by novel skin electroporation device protects mice against intranasal poxvirus challenge. Vaccine 25, 1814–1823 (2007)

    PubMed  CAS  Google Scholar 

  83. Daugimont, L., Baron, N., Vandermeulen, G., Pavselj, N., Miklavcic, D., Jullien, M., et al.: Hollow microneedle arrays for intradermal drug delivery and DNA electroporation. J Membr Biol 236, 117–125 (2010)

    PubMed  CAS  Google Scholar 

  84. Levine, M.M., Sztein, M.B.: Vaccine development strategies for improving immunization: the role of modern immunology. Nat Immunol 5, 460–464 (2004)

    PubMed  CAS  Google Scholar 

  85. Soppimath, K.S., Aminabhavi, T.M., Kulkarni, A.R., Rudzinski, W.E.: Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70, 1–20 (2001)

    PubMed  CAS  Google Scholar 

  86. Delie, F., Blanco-Prieto, M.J.: Polymeric particulates to improve oral bioavailability of peptide drugs. Molecules 10, 65–80 (2005)

    PubMed  CAS  Google Scholar 

  87. McCarron, P.A., Donnelly, R.F., Marouf, W.: Celecoxib-loaded poly(D, L-lactide-co-glycolide) nanoparticles prepared using a novel and controllable combination of diffusion and emulsification steps as part of the salting-out procedure. J Microencapsul 23, 480–498 (2006)

    PubMed  CAS  Google Scholar 

  88. Eniola, A.O., Hammer, D.A.: Artificial polymeric cells for targeted drug delivery. J Control Release 87, 15–22 (2003)

    PubMed  CAS  Google Scholar 

  89. Jaganathan, K.S., Vyas, S.P.: Strong systemic and mucosal immune responses to surface-modified PLGA microspheres containing recombinant hepatitis B antigen administered intranasally. Vaccine 24, 201–4211 (2006)

    Google Scholar 

  90. Gutierro, I., Hernandez, R.M., Igartua, M., Gascon, A.R., Pedraz, J.L.: Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine 21, 67–77 (2002)

    PubMed  CAS  Google Scholar 

  91. Lu, D., Garcia-Contreras, L., Xu, D., Kurtz, S.L., Liu, J., Braunstein, M., et al.: Poly (lactide-co-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen 85B. Pharm Res 24, 1834–1843 (2007)

    PubMed  CAS  Google Scholar 

  92. Sharp, F.A., Ruane, D., Claass, B., Creagh, E., Harris, J., Malyala, P., et al.: Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl. Acad. Sci. U. S. A. 106, 870–875 (2009)

    PubMed  CAS  Google Scholar 

  93. de Jalon, E.G., Blanco-Prieto, M.J., Ygartua, P., Santoyo, S.: PLGA microparticles: possible vehicles for topical drug delivery. Int J Pharm 226, 181–184 (2001)

    PubMed  Google Scholar 

  94. Jenning, V., Gysler, A., Schafer-Korting, M., Gohla, S.H.: Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm 49, 211–218 (2000)

    PubMed  CAS  Google Scholar 

  95. Alvarez-Roman, R., Naik, A., Kalia, Y.N., Guy, R.H., Fessi, H.: Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res 21, 1818–1825 (2004)

    PubMed  CAS  Google Scholar 

  96. Alvarez-Roman, R., Naik, A., Kalia, Y.N., Guy, R.H., Fessi, H.: Skin penetration and distribution of polymeric nanoparticles. J Control Release 99, 53–62 (2004)

    PubMed  CAS  Google Scholar 

  97. Luengo, J., Weiss, B., Schneider, M., Ehlers, A., Stracke, F., Konig, K., et al.: Influence of nanoencapsulation on human skin transport of flufenamic acid. Skin Pharmacol Physiol 19, 190–197 (2006)

    PubMed  CAS  Google Scholar 

  98. Lademann, J., Richter, H., Teichmann, A., Otberg, N., Blume-Peytavi, U., Luengo, J., et al.: Nanoparticles–an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 66, 159–164 (2007)

    PubMed  CAS  Google Scholar 

  99. Toll, R., Jacobi, U., Richter, H., Lademann, J., Schaefer, H., Blume-Peytavi, U.: Penetration profile of microspheres in follicular targeting of terminal hair follicles. J Invest Dermatol 123, 168–176 (2004)

    PubMed  CAS  Google Scholar 

  100. Coulman, S.A., Anstey, A., Gateley, C., Morrissey, A., McLoughlin, P., Allender, C., et al.: Microneedle mediated delivery of nanoparticles into human skin. Int J Pharm Jan. 366, 190–200 (2009)

    CAS  Google Scholar 

  101. McAllister, D.V., Wang, P.M., Davis, S.P., Park, J.H., Canatella, P.J., Allen, M.G., et al.: Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc. Natl. Acad. Sci. U. S. A. 100, 13755–13760 (2003)

    PubMed  CAS  Google Scholar 

  102. Bal, S.M., Slutter, B., Jiskoot, W., Bouwstra, J.A.: Small is beautiful: N-trimethyl chitosan-ovalbumin conjugates for microneedle-based transcutaneous immunisation. Vaccine 29, 4025–4032 (2011)

    PubMed  CAS  Google Scholar 

  103. Ueno, H., Schmitt, N., Klechevsky, E., Pedroza-Gonzalez, A., Matsui, T., Zurawski, G., et al.: Harnessing human dendritic cell subsets for medicine. Immunol Rev 234, 199–212 (2010)

    PubMed  CAS  Google Scholar 

  104. Birchall, J.C., Clemo, R., Anstey, A., John, D.N.: Microneedles in clinical practice–an exploratory study into the opinions of healthcare professionals and the public. Pharm Res 28, 95–106 (2011)

    PubMed  CAS  Google Scholar 

  105. Donnelly, R.F., Singh, T.R., Tunney, M.M., Morrow, D.I., McCarron, P.A., O’Mahony, C., Woolfson, A.D.: Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro. Pharm Res 26, 2513–2522 (2009)

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, Queen’s University Belfast, Belfast, UK

    Ryan F. Donnelly PhD, Sharifa Al-Zahrani BSc, Cian M. McCrudden PhD & Cristopher J. Scott PhD

  2. Centre for Infection and Immunology, Queen’s University Belfast, Belfast, UK

    Marija Zaric MB & Adrien Kissenpfenning PhD

Authors
  1. Ryan F. Donnelly PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharifa Al-Zahrani BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marija Zaric MB
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cian M. McCrudden PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristopher J. Scott PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adrien Kissenpfenning PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryan F. Donnelly PhD .

Editor information

Editors and Affiliations

  1. Institute for Molecular Vaccines, Heidelberg, Germany

    Matthias Giese

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Donnelly, R.F., Al-Zahrani, S., Zaric, M., McCrudden, C.M., Scott, C.J., Kissenpfenning, A. (2014). Vaccine Delivery Using Microneedles. In: Giese, M. (eds) Molecular Vaccines. Springer, Cham. https://doi.org/10.1007/978-3-319-00978-0_17

Download citation

Publish with us

Policies and ethics

Search

Navigation