Nano- and microspheres as potential nasal antigen delivery system : application to influenza virus antigen

The aim of this thesis was to evaluate the potential of poly(D,L-lactide-co-glycolide) and alginate particles as nasal delivery system for antigen, using influenza virus antigen as a model. This work is ase on the hypothesis that polymeric particles ( The study was divided in three major steps. The first step was to formulate poly(D,L-lactide-co-glycolide) and alginate particles. The formulation, which is essential during the development of an antigen delivery system, comprised the polymeric particle preparation and characterization/ the former included the analysis of the particle morphology, the determination of the particle size and size distribution, the study of the particle biodegradation, the determination of the protein loading, the verification of the polymer molecular weight and antigenicity of encapsulated antigen, and the in vitro antigen release. The second step was to evaluate the potential of these poly(D,L-lactide-co-glycolide) and alginate particles to enhance the immune responses to influenza virus antigen. The particles were administrered intranaslly to mice and the nasal washes IgA and serum IgG responses were investigated. The third step was to try to explain the induced immune responses. The poly(D,L-lactide-co-glycolide) and alginate particles were labelled with a fluorescent marker. Their fate after intranasal administration to mice was investigated. The approach of immunization using polymeric particles is discussed with a critical approachThèse de doctorat en sciences pharmaceutiques -- UCL, 199