Novel Formulation Concept for Particulate Uptake of Vaccines via the Nasal Associated Lymphoid Tissue

Abstract

Aerosol vaccination via the mucosa targets an epithelium critical to host defence against inhaled pathogens, potentially avoids needle injection, and provides an exciting opportunity in the development of stable dry powder vaccine formulations. Specialised cells in the mucosa are able to take up and guide antigens directly to immune cells. In contrast to soluble antigen formulations, particles with antigen also provoke a local sIgA mediated immune response before being presented to the systemic immune system. In this study, particles containing the model antigen BSA and chitosan as stabiliser with adjuvant activity are produced by spray drying. The compatibility and uptake of these particles via the respiratory epithelium is determined in vitro on Calu-3 cells. The in vitro deposition studies are performed in a nasal cast made from CT scan data using a novel nasal dry powder device. The deposition profile is optimised by the use of interactive mixtures with a low separation capacity. The spray drying process results in spherical particles with a size in the low micrometer range (x50 3μm), which are well tolerated when administered to the cells and which are readily taken up. As the particles have to be big enough to be retained in the appropriate place in the respiratory tract (e.g. the nasal cavity) to be taken up efficiently, the primary particles are too small. Deposition studies show a high fraction of almost 56% transiting the nose and being capable of inhalation. This fraction can be reduced by utilising an interactive mixture with a carrier, where only 5% of the antigen carrying particles leave the nasal cavity. Particulate vaccine formulations are a promising formulation approach for mucosal vaccination targeting the nasal mucosa. With small antigen carrying particles immobilised on carrier particles, the antigen is delivered exclusively to the nose.