Stabilization of Aerosolizable Nano-carriers by Freeze-Drying

This study investigates the feasibility of freeze-drying aerosolizable nano-carriers (NC) by the use of different lyoprotective agents (LPA) and the influence of the freeze-drying on the physicochemical properties of these nano-carriers and on their aerosolization. Nano-carriers were prepared from fast-degrading polymers, DMAPA(24)-PVAL-g-PLGA(1:7.5) and DEAPA(26)-PVAL-g-PLGA(1:10), and freeze-dried using increasing concentrations of different LPA. The hydrodynamic diameter, zeta potential and morphology (atomic force microscopy) of NC were characterized before and after freeze-drying. The ability to aerosolize using a jet nebulizer and an electronic micro-pump nebulizer was also investigated. Freeze-drying with LPA led to a decreased zeta-potential of NC and changes in size about 20 nm without alteration in shape, whereas lyophilizates without LPA were found to aggregate. While freeze-drying was positively affected by increasing concentrations, it was not influenced by the type of LPA. The possibility for aerosolization was not influenced by any LPA. Freeze-drying with LPA is a suitable method to physically stabilize fast-degrading NC from aqueous suspensions without influencing the aerosolizability.