The potential for the noninvasive delivery of polymeric nanocarriers using propellant-based inhalers in the treatment of Chlamydial respiratory infections

A novel strategy for pulmonary delivery of polymeric nanocarriers (NCs) pressurized-metered dose inhalers (pMDIs) is reported in this work. Core–shell particles consisting of a water soluble, hydrofluoroalkane(HFA)-philic biodegradable copolymer of chitosan and poly(lactic acid), and a core of poly(d,l-lactide-co-glycolide) (PLGA) NCs were prepared by a modified emulsification–diffusion methodology. Dispersions of the core–shell particles in HFA propellant revealed enhanced physical stability compared to polymeric NCs alone, and more importantly, excellent aerosol characteristics as determined by inertial impaction studies. Confocal microscopy revealed that the polymeric NCs from such core–shell particles are capable not only to be taken up by Calu-3 (airway epithelial) cells that have been infected with Chlamydia pneumoniae, an intracellular pathogen, but are also internalized within chlamydial inclusions. Our results suggest that the proposed methodology can be used as a general platform for the delivery of polymeric NCs to the respiratory tract using the inexpensive pMDIs, and that such an approach may be used to target and deliver drugs to treat chlamydial-related infections.