Surfactant-free redispersible nanoparticles in fast-dissolving composite microcarriers for dry-powder inhalation

Spray-drying was investigated for the stabilization of surfactant-free nanoparticles as carriers for dry-powder inhalers. The microparticles rapidly dissolve after inhalation yielding dispersed nanoparticles.Nanoparticles were prepared by a solvent displacement technique avoiding any surfactants. Microcarriers were prepared by spray-drying nanoparticle suspensions with lactose, mannitol or α-cyclodextrin as stabilizers. Nanoparticle size and ζ-potential before and after spray-drying were analyzed with photon correlation spectroscopy and laser Doppler anemometry, respectively. Cell uptake into macrophages was studied using U 937 cells by confocal microscopy.Stabilization of nanoparticle suspensions by spray-drying with α-cyclodextrin yielded redispersible particles smaller than 200 nm. α-Cyclodextrin was a more efficient stabilizer than commonly used excipients. Microparticles with a mass median aerodynamic diameter of 4.3 μm showed properties suitable for dry-powder inhalation. The cell culture experiments with redispersed nanoparticles seem to suggest less interaction and uptake with macrophages compared to polymeric microparticles.In conclusion, nanoparticles can easily be transferred to dry-powders suitable for inhalation by spray-drying. This allows the pulmonary application of nanoparticles in high concentrations.

Stabilization of PLGA-nanoparticle suspensions by spray-drying with α-cyclodextrin yielded microcarriers suitable for inhalation. Upon addition of water the carrier disintegrate into redispersible particles smaller than 200 nm.Figure optionsDownload as PowerPoint slide