Pulmonary Administration of PEGylated Polylysine Dendrimers: Absorption from the Lung versus Retention within the Lung Is Highly Size-Dependent

The systemic delivery of drugs via the inhaled route is an attractive, needle-free means of improving the systemic exposure of molecules such as peptides and proteins that are poorly absorbed after oral administration. Directed delivery into the lungs also provides a means of increasing drug concentrations at the site of action for lung-specific disease states such as pulmonary infections and lung cancer. The current study has examined the potential utility of PEGylated polylysine dendrimers as pulmonary delivery agents and in particular sought to explore the relationship between dendrimer size and absorption of the intact construct (as a potential systemic delivery mechanism) versus retention within the lungs (as a potential pulmonary depot for controlled local release). Dendrimer absorption from the lungs was inversely correlated with molecular weight, with approximately 20–30% of the dose of relatively small (