Biodistribution and Cellular Uptake Upon Intranasal Administration of Monodisperse Biodegradable Particles

Size and chemistry are known to play an important role in particle biodistribution and cellular uptake. The synthesis of monodisperse biodegradable polyanhydride particles of multiple sizes have enabled us to systematically evaluate the role of initial particle size and chemistry on biodistribution and trafficking. In this work we used a murine model to evaluate the biodistribution of intranasally administered 200 nm, 400 nm, and 1.5 µm (nominal size) poly(sebacic acid) particles and commercial polystyrene particles of the same size. The biodistribution of these particles was evaluated using fluorescent imaging of excised organs one day and seven days post administration. Cellular uptake was evaluated for the lung and lymph nodes by labeling tissue homogenates for specific cell types. While all three particle sizes are present in the lungs one day after administration, the quantity of 200 and 400 nm particles present, as determined through mean fluorescence intensity, was greater than the 1.5 µm particles. The percentage of neutrophils, macrophages, dendritic cells and epithelial cells with particles was also found to be dependent upon the size and chemistry of the particle. The insights gained from these studies will enable the rational design of nanoparticle-based adjuvants and delivery systems for vaccines against respiratory pathogens.