Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 78, Issue 1, Pages 90-96Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2010.12.002
Keywords
Redispersible biodegradable nanoparticles; Poly (lactide-co-glycolide); Spray-drying; Microparticies; Dry-powder inhalation
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Funding
- German Ministry of Education and Research (BMBF) [13N8888]
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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 alpha-cyclodextrin as stabilizers. Nanoparticle size and zeta-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 alpha-cyclodextrin yielded redispersible particles smaller than 200 nm. alpha-Cyclodextrin was a more efficient stabilizer than commonly used excipients. Microparticles with a mass median aerodynamic diameter of 4.3 mu m 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. (C) 2010 Elsevier B.V. All rights reserved.
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