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.

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

“…High ratio of surface area to volume Interactions between the groups of the polymer and drug molecule, such as electrostatic, and H-bonding Production of a microenvironment with special lower polarity inside the nanoparticles than in the aqueous bulk phase [79][80][81][82][83] Mucociliary clearance and short residence time Localization of the formulation for a longer time Enhancement of contact time inside the nasal cavity [84][85][86] Poor penetration for large and hydrophilic molecules Ability to open up tight junctions Possibility of high endocytosis Ability to change mucosal membrane properties [87,88] Enzymatic…”

Porous Maltodextrin-Based Nanoparticles: A Safe Delivery System for Nasal Vaccines

“…NPL can be loaded with large amounts of proteins or antigens [5,13] and act as an efficient delivery system. Upon nasal administration, NPL enter the cells by endocytosis and return to the lumen through exocytosis [13], without crossing the first epithelial cell layer [9]. During this cellular journey, NPL deliver their cargo of antigens, the first step in triggering an immune response.…”

“…The cellular viability was studied in two epithelial cellular models representative of the main types of cells that NPL would encounter after nasal administration [9]; it was determined using a nanoparticle concentration range of 0 to 150 μg/cm 2 with a combination of MTT and LDH assays. In airway epithelial H292 cells, the viability did not decrease after NPL treatment and a slight increase was even observed (Figure 2(a)).…”

“…After intranasal administration, NPL entered the epithelial cells to deliver the antigens and were exocytosed. They were finally swallowed and totally eliminated within 3 days via the intestinal tract [9]. Furthermore, biodistribution analyses did not show any evidence of passage into blood or lymph, thus precluding organ accumulation [9].…”

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

“…Up to now, the only nasal immortal cell line of human origin available has been the RPMI 2650 cell line (Bai et al, 2008). However, other cell lines have been used for nasal application: Calu-3 and 16HBE (Bernocchi et al, 2016). Interestingly, heterogeneous tissues can be constructed from immortalized cells by developing co-cultures (e.g.…”