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Macroflux® Microprojection Array Patch Technology: A New and Efficient Approach for Intracutaneous Immunization

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Abstract

Purpose. We evaluated the Macroflux® microprojection array patch technology as a novel system for intracutaneous delivery of protein antigens.

Methods. Macroflux® microprojection array systems (330-μm microprojection length, 190 microprojections/cm2, 1- and 2-cm2 area) were coated with a model protein antigen, ovalbumin (OVA), to produce a dry-film coating. After system application, microprojection penetration depth, OVA delivery, and comparative immune responses were evaluated in a hairless guinea pig model.

Results. Macroflux® microprojections penetrated into hairless guinea pig skin at an average depth of 100 μm with no projections deeper than 300 μm. Doses of 1 to 80 μg of OVA were delivered via 1- or 2-cm2 systems by varying the coating solution concentration and wearing time. Delivery rates were as high as 20 μg in 5 s. In a prime and boost dose immune response study, OVA-coated Macroflux® was most comparable to equivalent doses injected intradermally. Higher antibody titers were observed when OVA was administered with the microprojection array or intradermally at low doses (1 and 5 μg). Macroflux® administration at 1- and 5-μg doses gave immune responses up to 50-fold greater than that observed after the same subcutaneous or intramuscular dose. Dry coating an adjuvant, glucosaminyl muramyl dipeptide, with OVA on the Macroflux® resulted in augmented antibody responses.

Conclusions. Macroflux® skin patch technology provides rapid and reproducible intracutaneous administration of dry-coated antigen. The depth of skin penetration targets skin immune cells; the quantity of antigen delivered can be controlled by formulation, patch wearing time, and system size. This novel needle-free patch technology may ultimately have broad applications for a wide variety of therapeutic vaccines to improve efficacy and convenience of use.

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REFERENCES

  1. J. D. Bos. Skin Immune System (SIS). Cutaneous Immunology and Clinical Immunodermatology CRC Press, New York, 1997.

    Google Scholar 

  2. K. E. Fichtelius, O. Groth, and S. Liden. The skin, a first level lymphoid organ? Int. Arch. Allergy Appl. Immunol. 37:607–620 (1970).

    Google Scholar 

  3. R. C. Yu, D. C. Abrams, M. Alaibac, and A. C. Chu. Morphological and quantitative analysis of normal epidermal Langerhans cells using confocal scanning laser microscopy. Br. J. Dermatol. 131:843–848 (1994).

    Google Scholar 

  4. J. H. Brooks, L. H. Criep, and F. L. Ruben. Intradermal administration of bivalent and monovalent influenza vaccines. Ann. Allergy 39:110–112 (1977).

    Google Scholar 

  5. W. Halperin, W. I. Weiss, R. Altman, M. A. Diamond, K. J. Black, A. W. Iaci, H. C. Black, and M. Goldfield. A comparison of the intradermal and subcutaneous routes of influenza vaccination with a/new jersey/76 (swine flu) and a/victoria/75: Report of a study and review of the literature. Am. J. Public Health 69:1247–1250 (1979).

    Google Scholar 

  6. E. A. Henderson, T. J. Louie, K. Ramotar, D. Ledgerwood, K. M. Hope, and A. Kennedy. Comparison of higher-dose intradermal hepatitis B vaccination to standard intramuscular vaccination of health care workers. Infect. Control Hosp. Epidemiol. 21:264–269 (2000).

    Google Scholar 

  7. T. Propst, A. Propst, K. Lhotta, W. Vogel, and P. Konig. Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination. Am. J. Kidney Dis. 32:1041–1045 (1998).

    Google Scholar 

  8. R. Panchagnula, K. Stemmer, and W. A. Ritschel. Animal models for transdermal drug delivery. Methods Find. Exp. Clin. Pharmacol. 19:335–341 (1997).

    Google Scholar 

  9. H. Sueki, C. Gammal, K. Kudoh, and A. M. Kligman. Hairless guinea pig skin: Anatomical basis for studies of cutaneous biology. Eur. J. Dermatol. 10:357–364 (2000).

    Google Scholar 

  10. S. Kumar, H. Char, S. Patel, D. Piemontese, K. Iqbal, A. W. Malick, E. Neugroschel, and C. R. Behl. Effect of iontophoresis on in vitro skin permeation of an analogue of growth hormone releasing factor in the hairless guinea pig model. J. Pharm. Sci. 81:635–639 (1992).

    Google Scholar 

  11. K. C. Moon, R. C. Wester, and H. I. Maibach. Diseased skin models in the hairless guinea pig skin: In vivo percutaneous absorption. Dermatologica 180:8–12 (1990).

    Google Scholar 

  12. T. Horio, H. Miyauchi, and Y. Asada. The hairless guinea pig as an experimental animal in photodermatology. Photodermatol. Photoimmunol. Photomed. 8:69–72 (1991).

    Google Scholar 

  13. P. J. Bobrowski, R. Capiola, and Y. M. Centifanto. Latent herpes simplex virus reactivation in the guinea pig. An animal model for recurrent disease. Int. J Dermatol. 30:29–35 (1991).

    Google Scholar 

  14. S. K. Brantley, S. F. Davidson, and S. K. Das. A dose-related curve of wound tensile strength following ultraviolet irradiation in the hairless guinea pig. Am. J. Med. Sci. 302:75–81 (1991).

    Google Scholar 

  15. A. Fullerton and J. Serup. Topical D-vitamins: Multiparametric comparison of the irritant potential of calcipotriol, tacalcitol, and calcitriol in a hairless guinea pig model. Contact Dermatitis 36: 184–190 (1997).

    Google Scholar 

  16. P. W. Lowry, C. Sabella, C. M. Koropchak, B. N. Watson, H. M. Thackray, G. M. Abbruzzi, and A. M. Arvin. Investigation of the pathogenesis of varicella-zoster virus infection in guinea pigs by using polymerase chain reaction. J. Infect. Dis. 16:78–83 (1993).

    Google Scholar 

  17. D. L. Ruble, J. J. Elliot, D. M. Waag, and G. P. Jaax. A refined guinea pig model for evaluated delayed-type hypersensitivity reaction caused by Q fever vaccines. Lab. Anim. Sci. 44:608–612 (1994).

    Google Scholar 

  18. H. Miyauchi and T. Horio. A new animal model for contact dermatitis: The hairless guinea pig. J. Dermatol. 19:140–145 (1992).

    Google Scholar 

  19. D. F. Woodward, A. L. Nieves, L. S. Williams, C. S. Spada, S. B. Hawley, and J. L. Duenes. A new hairless strain of guinea pig: Characterization of the cutaneous morphology and pharmacology. In H. I. Maibach and N. J. Lowe, (eds.), Models in Dermatology Vol. 4, Karger, Basel 1989, pp. 71–78.

    Google Scholar 

  20. M. Cormier, A. P. Neukermans, B. Block, F. T. Theeuwes, and A. A. Amkraut. Device for enhancing transdermal agent delivery or sampling. European Patent 0914178, 1999.

  21. A. Enk and S. Katz. Early molecular events in the induction phase of contact sensitivity. Proc. Natl. Acad. Sci. USA 89:1398–1402 (1992).

    Google Scholar 

  22. H. Fan, Q. Lin, G. R. Morrissey, and P. A. Khavari. Immunization via hair follicles by topical application of naked DNA to normal skin. Nat. Biotechnol. 17:870–872 (1999).

    Google Scholar 

  23. G. M. Glenn, M. Rao, G. R. Matyas, and C. R. Alving. Skin immunization made possible by cholera toxin. Nature 391:851 (1998).

    Google Scholar 

  24. N. Puri, E. H. Weyand, S. M. Abdel-Rahman, and P. J. Sinko. An investigation on the intradermal route as an effective means of immunization for microparticulate vaccine delivery systems. Vaccine 18:2600–2612 (2000).

    Google Scholar 

  25. C. A. Herrick, H. MacLeod, E. Glusac, R. E. Tigelaar, and K. Bottomly. Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J. Clin. Invest. 105:765–775 (2000).

    Google Scholar 

  26. L. F. Wang, J. Y. Lin, K. H. Hsieh, and R. H. Lin. Epicutaneous exposure of protein antigen induces a predominant Th2-like response with high IgE production in mice. J. Immunol. 156:4077–4082 (1996).

    Google Scholar 

  27. D. C. Tang, Z. Shi, and D. T. Curiel. Vaccination onto bare skin. Nature 388:729–730 (1997).

    Google Scholar 

  28. G. M. Glenn, D. N. Taylor, X. Li, S. Frankel, A. Montemarano, and C. R. Alving. Transcutaneous immunization: A human vaccine delivery strategy using a patch. Nat. Med. 6:1403–1406 (2000).

    Google Scholar 

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Correspondence to James A. Matriano.

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Matriano, J.A., Cormier, M., Johnson, J. et al. Macroflux® Microprojection Array Patch Technology: A New and Efficient Approach for Intracutaneous Immunization. Pharm Res 19, 63–70 (2002). https://doi.org/10.1023/A:1013607400040

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  • DOI: https://doi.org/10.1023/A:1013607400040

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