期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 25, 期 4-5, 页码 427-437出版社
ELSEVIER
DOI: 10.1016/j.ejps.2005.04.009
关键词
chitosan nanoparticles; dry powders; ionic gelation; microspheres; pulmonary protein delivery; spray drying
It has already been demonstrated that spray drying is a very valuable technique for producing dry powders adequate for pulmonary delivery of drugs. We have developed chitosan/tripolyphosphate nanoparticles that promote peptide absorption across mucosal surfaces. The aim of this work was to microencapsulate protein-loaded chitosan nanoparticles using typical aerosol excipients, such as mannitol and lactose, producing microspheres as carriers of protein-loaded nanoparticles to the lung. The results showed that the obtained microspheres are mostly spherical and possess appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters between 2 and 3 pm, apparent density lower than 0.45 g/cm(3)). Moreover, microspheres morphology was strongly affected by the content of chitosan nanoparticles. These nanoparticles show a good protein loading capacity (65-80%), providing the release of 75-80% insulin within 15min, and can be easily recovered from microspheres after contact with an aqueous medium with no significant changes in their size and zeta potential values. Therefore, this work demonstrated that protein-loaded nanoparticles could be successfully incorporated into microspheres with adequate characteristics to reach the deep lung, which after contact with its aqueous environment are expected to be able to release the nanoparticles, and thus, the therapeutic macromolecule. (c) 2005 Elsevier B.V. All rights reserved.
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