Mechanisms allowing protein delivery in nasal mucosa using NPL nanoparticles

JOURNAL OF CONTROLLED RELEASE

卷:232

Article

Bernocchi, B.^1,2,3  Carpentier, R.^1,2,3  Lantier, I.^5,6,7  Ducournau, C.^5,6,7  Dimier-Poisson, I.^5,6,7  Betbeder, D.^1,2,3,4 

[1] INSERM, LIRIC, UMR 995, F-59000 Lille, France

[2] Univ Lille, LIRIC, UMR 995, F-59000 Lille, France

[3] CHRU Lille, LIRIC, UMR 995, F-59000 Lille, France

[4] Univ Artois, F-62000 Arras, France

[5] INRA, Infectiol & Sante Publ UMR1282, F-37380 Nouzilly, France

[6] Lab Expertise Infect Anim, Montpellier, France

[7] Univ Tours, Infectiol & Sante Publ UMR1282, F-37000 Tours, France

关键词: Nanoparticle;    Intranasal drug delivery;    Protein delivery;    Transcytosis;    Biodistribution;    Vaccine;   

DOI  :  10.1016/j.jconrel.2016.04.014

来源: Elsevier

【 摘 要 】

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. (C) 2016 The Authors. Published by Elsevier B.V.

【 授权许可】

Free