Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation, in vitro and in vivo characterization.

Large porous particles (LPPs) could be used as a useful carrier for non-invasive delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX-LPPs) can help to eliminate the highly complicated and harmful solvent used in PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter (MMAD) of 5.74 ± 0.09 μm, high encapsulation efficiency and good aerosolisation properties were produced using ammonium bicarbonate as porogen. Cytotoxicity of PTX-LPPs on A549 and Calu-6 cell lines was comparable with Free-PTX. Endotracheal administration of PTX-LPPs in rats exhibited PTX plasma concentration in the therapeutic range which lasted 4-fold longer than i.v. injection. The bioavailability was measured as 51 ± 7.1%. The lung targeting efficiency (Te) of PTX-LPPs was 11.9-fold higher than i.v. administration. PTX-LPPs could deliver a higher PTX to lung with a non-toxic plasma level in a longer duration which shows their pulmonary delivery suitability.