title: Parameter optimization toward optimal microneedle-based dermal vaccination.
abstract: Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles. Microneedles are used to deliver a drug into the skin in a minimally-invasive and potentially pain free manner. Besides, the skin is a potent immune organ that is highly suitable for vaccination. However, there are several factors that influence the penetration ability of the skin by microneedles and the immune responses upon microneedle-based immunization. In this study we assessed several different microneedle arrays for their ability to penetrate ex vivo human skin by using trypan blue and (fluorescently or radioactively labeled) ovalbumin. Next, these different microneedles and several factors, including the dose of ovalbumin, the effect of using an impact-insertion applicator, skin location of microneedle application, and the area of microneedle application, were tested in vivo in mice. The penetration ability and the dose of ovalbumin that is delivered into the skin were shown to be dependent on the use of an applicator and on the microneedle geometry and size of the array. Besides microneedle penetration, the above described factors influenced the immune responses upon microneedle-based vaccination in vivo. It was shown that the ovalbumin-specific antibody responses upon microneedle-based vaccination could be increased up to 12-fold when an impact-insertion applicator was used, up to 8-fold when microneedles were applied over a larger surface area, and up to 36-fold dependent on the location of microneedle application. Therefore, these influencing factors should be considered to optimize microneedle-based dermal immunization technologies.
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: van der Maaden
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Eleni Maria
authors.initials: EM
authors.lastname: Varypataki
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Huixin
authors.initials: H
authors.lastname: Yu
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Romeijn
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. Electronic address: bouwstra@lacdr.leidenuniv.nl.
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections / Q000295:instrumentation*; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D014611:Vaccination / Q000295:instrumentation* / Q000379:methods
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D010047:Ovalbumin
keywords: (Trans)dermal drug delivery; Microneedles; Vaccine delivery