title: Layer-by-Layer Assembly of Inactivated Poliovirus and N-Trimethyl Chitosan on pH-Sensitive Microneedles for Dermal Vaccination.
abstract: The aim of this work was to coat pH-sensitive microneedle arrays with inactivated polio vaccine (IPV) particles and N-trimethyl chitosan chloride (TMC) via electrostatic interactions, and assess the immunogenicity of the vaccine after topical application of the coated microneedles in rats. The surface of 200 μm long microneedles was first chemically modified with pH-sensitive (pyridine) groups and then coated with negatively charged IPV and a positively charged polymer (TMC). To obtain a sufficient high antigen dose, 10 layers of IPV were alternately coated with TMC. The binding of IPV and TMC onto pH-sensitive microneedles was quantified and visualized by using fluorescently labeled TMC and IPV. The release of IPV and TMC from the microneedles was evaluated in ex vivo human skin by fluorescence and the immunogenicity of (unlabeled) IPV was assessed after topical application of the coated microneedles in rats. pH-sensitive microneedles were homogeneously coated with 10 layers of both IPV and TMC, resulting in 45 D antigen units IPV and 700 ng TMC per microneedle array. Fluorescence microscopy imaging revealed that both IPV and TMC were released into ex vivo human skin upon application of the coated microneedles. Finally, in vivo application of IPV-TMC-coated pH-sensitive microneedles in rats led to the induction of IPV specific antibody responses, illustrating that they are practically applicable. Topical administration of pH-sensitive microneedles coated with polyelectrolyte multinanolayers of antigens and oppositely charged polymers may be a useful approach for microneedle-based vaccination.
authors.affiliation: †Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300 RA, 2311 EZ 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 2300 RA, 2311 EZ Leiden, The Netherlands.
authors.forename: Emine
authors.initials: E
authors.lastname: Sekerdag
authors.affiliation: †Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300 RA, 2311 EZ Leiden, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: Schipper
authors.affiliation: †Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300 RA, 2311 EZ Leiden, The Netherlands.|‡Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Gideon
authors.initials: G
authors.lastname: Kersten
authors.affiliation: †Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300 RA, 2311 EZ 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 2300 RA, 2311 EZ Leiden, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008845:Microinjections; D008856:Microscopy, Fluorescence; D009339:Needles; D017955:Poliovirus / Q000737:chemistry*; D023321:Poliovirus Vaccines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000737:chemistry*; D014611:Vaccination
chemical_list: C118071:N-trimethyl chitosan chloride; D023321:Poliovirus Vaccines; D048271:Chitosan