Inhalable nano into micro dry powders for ivacaftor delivery: The role of mannitol and cysteamine as mucus-active agents

In this paper the innovative approach of Nano into micro (NiM9 was developed to produce Nanoparticles loaded Ivacaftor to incorporate into mannitol or mannitol/cysteamine micromatrices for drug pulmonary administration in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing a loading of Ivacaftor of 15.5 % w/w were produced. These Nanoparticles were incorporated into microparticles to obtain NiM that were characterized in terms of size and size distribution, interaction with CF-AM by rheological and turbidimetric studies as well as by aerodynamic diameter measurements. Finally the activity of Ivacaftor into these NiM was evaluated by in vitro preliminary experiments. NiM at matrix composed by a mixture of mannitol:cysteamine showed greater ability to reduce CF-AM viscosity whereas that based on just mannitol showed the better aerodynamic properties with a FRF of about 25 %. All produced NiM showed very good cytocompatibility and released Ivacaftor showed to be able to restore the chroride transport in vitro.