Journal
JOURNAL OF CONTROLLED RELEASE
Volume 157, Issue 3, Pages 383-390Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2011.08.008
Keywords
Chitosan nanoparticles; Dry powders; In vivo administration; Lung distribution; Pulmonary protein delivery
Funding
- European Union [013882 of call FP6-2003-NMP-TI-3-Main]
- Spanish Government [PS09/00816]
- XUNTA de Galicia [09CSA022203PR, 2010/18-FEDER]
- Portuguese Foundation for Science and Technology [PTDC/SAU-FCF/100291/2008]
- IBB/CBME, LA
- Spanish Agency of International Cooperation and Development
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This work presents a new dry powder system consisting of microencapsulated protein-loaded chitosan nanoparticles (CS NPs). The developed system was evaluated in vivo in rats in order to investigate its potential to transport insulin (INS), a model protein, to the deep lung, where it is absorbed into systemic circulation. The INS-loaded CS NPs were prepared by ionotropic gelation and characterized for morphology, size, zeta potential, association efficiency and loading capacity. Afterwards, the NPs were co-spray dried with mannitol resulting in a dry powder with adequate aerodynamic properties for deposition in deep lungs. The assessment of the plasmatic glucose levels following intratracheal administration to rats revealed that the microencapsulated INS-loaded CS NPs induced a more pronounced and prolonged hypoglycemic effect compared to the controls. Accordingly, the developed system constitutes a promising alternative to systemically deliver therapeutic macromolecules to the lungs, but it can also be used to provide a local effect. (C) 2011 Elsevier B. V. All rights reserved.
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