title: Mechanisms allowing protein delivery in nasal mucosa using NPL nanoparticles.
abstract: The intranasal administration of proteins using nanoparticles is a promising approach for several applications, especially for mucosal vaccines. Delivery of protein within the epithelial barrier is a key point to elicit an immune response and nano-carrier has to show no toxicity. The aim of this work was to elucidate the interactions of cationic porous nanoparticles loaded with protein delivery for antigen delivery in the nose. We investigated the loading, the cellular delivery and the epithelial transcytosis of proteins associated to these nanoparticles containing an anionic lipid in their core (NPL). NPL were highly endocytosed by airway epithelial cells and significantly improved the protein delivery into the cell. In vitro transcytosis studies showed that NPL did not modify the in vitro epithelial permeability suggesting no toxicity of these carriers. Moreover protein and NPL did not translocate the epithelial barrier. In vivo studies demonstrated that NPL prolonged the nasal residence time of the protein and no NPL were found beyond the epithelial barrier in vivo, precluding a negative side effect. All together these results establish the NPL as a bio-eliminable and optimal vaccine carrier.
authors.affiliation: Inserm, LIRIC-UMR 995, F-59000 Lille, France; Université de Lille, LIRIC-UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC-UMR 995, F-59000 Lille, France.
authors.forename: B
authors.initials: B
authors.lastname: Bernocchi
authors.affiliation: Inserm, LIRIC-UMR 995, F-59000 Lille, France; Université de Lille, LIRIC-UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC-UMR 995, F-59000 Lille, France. Electronic address: rodolphe.carpentier@univ-lille2.fr.
authors.forename: R
authors.initials: R
authors.lastname: Carpentier
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France. Laboratoire d'Expertise en Infection Animale; Université François-Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France. Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses.
authors.forename: I
authors.initials: I
authors.lastname: Lantier
authors.affiliation: Université François-Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France. Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France. Laboratoire d'Expertise en Infection Animale.
authors.forename: C
authors.initials: C
authors.lastname: Ducournau
authors.affiliation: Université François-Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France. Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France. Laboratoire d'Expertise en Infection Animale.
authors.forename: I
authors.initials: I
authors.lastname: Dimier-Poisson
authors.affiliation: Inserm, LIRIC-UMR 995, F-59000 Lille, France; Université de Lille, LIRIC-UMR 995, F-59000 Lille, France; CHRU de Lille, LIRIC-UMR 995, F-59000 Lille, France; University of Artois, 62000 Arras, France.
authors.forename: D
authors.initials: D
authors.lastname: Betbeder
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004705:Endocytosis; D004811:Epichlorohydrin / Q000008:administration & dosage / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
chemical_list: D000941:Antigens; D004337:Drug Carriers; D004852:Epoxy Compounds; D011134:Polysaccharides; D000644:Quaternary Ammonium Compounds; D004811:Epichlorohydrin; C045006:glycidyl trimethylammonium; C008315:maltodextrin; D010047:Ovalbumin
keywords: Biodistribution; Intranasal drug delivery; Nanoparticle; Protein delivery; Transcytosis; Vaccine