title: Feasibility study for intraepidermal delivery of proteins using a solid microneedle array.
abstract: Solid microneedles (MN) are a promising tool for dermal drug delivery. Particular focus lies on the field of vaccination due to pain-free, safe, hygienic and patient compliant antigen deposition. Diverse coating techniques and formulations have been developed to preserve vaccine activity and to enable targeted drug deposition in the skin. Process and long-term storage stability of coated MN, however, have not yet been studied in detail. Hence, a feasibility study was conducted determining the appropriate needle length (300 μm) for local intraepidermal protein delivery. Moreover, a protein-stabilizing coating formulation was developed. Coating of the MN resulted in protein concentrations between 10 and 23 μg, 90% of the bioactivity of the model protein asparaginase was maintained for 3 months. Skin experiments verified the intraepidermal deposition of 68.0 ± 11.7% of the coated model protein after single application. Slightly increased interleukin 8 levels right after MN insertion indicated minor skin irritation due to the mechanical piercing stress. Thus, specifically highlighting protein stabilization during storage, we demonstrated that selective intraepidermal deposition of proteins or peptides' using solid MN is a feasible approach.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Witting
authors.affiliation: Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Obst
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Pietzsch
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
authors.affiliation: Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany. Electronic address: sarah.hedtrich@fu-berlin.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hedtrich
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry; D001215:Asparaginase / Q000008:administration & dosage* / Q000737:chemistry; D005240:Feasibility Studies; D006801:Humans; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008845:Microinjections; D009339:Needles; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D013552:Swine
chemical_list: D000941:Antigens; D015850:Interleukin-6; D016209:Interleukin-8; D012710:Serum Albumin, Bovine; D001215:Asparaginase
keywords: Coating formulation; Human reconstructed skin; Protein stability; Proteins; Skin irritation; Solid microneedle array