title: Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays.
abstract: Targeting of vaccines to abundant immune cell populations within our outer thin skin layers using miniaturized devices-much thinner than a needle and syringe, could improve the efficacy of vaccines (and other immunotherapies). To meet this goal, a densely packed dissolving microprojection array (dissolving Nanopatch) is designed, achieving functional miniaturization by 1) formulating small microneedles (two orders of magnitude smaller than a standard needle and syringe) and 2) multiple layering of the payload within microprojections with tight tolerances (of the order of a micrometer). The formulation method is suitable to many vaccines because it is without harsh or complex chemical processes, and it is performed at low temperatures and at a neutral pH. When the formulated dNPs are applied to skin, consistent and robust penetration is achieved, rapidly targeting the skin strata of interest (<5 min; significantly faster than larger dissolving microneedles that have been previously reported). Resultant diffusion is significantly enhanced within the dermis compared with the epidermis. Using two different antigens (ovalbumin and a commercial trivalent influenza vaccine [Fluvax2008]), the administration of these dissolving patches generate robust systemic immune responses in a mouse model. To the authors' knowledge, this is the first report of successful vaccination with any form of dissolving microneedles. The patches made by this method therefore have the potential for pain-free, needle-free, and effective vaccination in humans.
authors.affiliation: The University of Queensland Australian Institute for Bioengineering and Nanotechnology (AIBN) Brisbane, QLD 4072, Australia.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Raphael
authors.forename: Tarl W
authors.initials: TW
authors.lastname: Prow
authors.forename: Michael L
authors.initials: ML
authors.lastname: Crichton
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D005260:Female; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry; D014611:Vaccination / Q000379:methods*
chemical_list: D004129:Dimethylpolysiloxanes; D007252:Influenza Vaccines; D010047:Ovalbumin; D002266:Carboxymethylcellulose Sodium