Title: Nanoparticle vaccines by inhalation
Description: Pulmonary vaccination has many potential advantages, however the development of needle-less vaccination for pulmonary delivery may require dry forms of vaccines whose powder properties allow for biocompatibility, low cost, heat and freeze tolerance, efficient aerosolization, and the ability to target cells of the immune system. For each of these reasons nanoparticles can play a critical role in the formulation, development and delivery of needle-less vaccination. The studies presented address the formulation and characterization of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with the CRM-197 and Hepatitis B surface antigens and their evaluation in animals. The work demonstrates how nanoparticles can be created easily using scalable solvent displacement methods and then loaded with antigen at sufficient levels (>5% w/w) for vaccine applications. Under appropriate low temperature conditions, and with a proper mix of excipients, these nanoparticles can be formulated into dry powder aerosols that have excellent safety, aerodynamic, and stability profiles. When administered to the pulmonary tract in animals, these vaccines invoke strong immune responses proving their feasibility as vaccine delivery vehicles. Finally, the approach detailed is extended to other polymer systems such to create novel aerosol forms. These forms open new avenues of engineering and thus represent a major step forward in the development of pulmonary delivery technologies.