Journal
JOURNAL OF CONTROLLED RELEASE
Volume 155, Issue 2, Pages 289-295Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2011.07.039
Keywords
Cystic fibrosis sputum; Gene delivery; Mannitol; Inhalable dry particles; Nanoparticles
Funding
- NCRR NIH HHS [TL1 RR025759] Funding Source: Medline
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1056997] Funding Source: National Science Foundation
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Cystic fibrosis (CF) sputum, a tenacious biopolymer network accumulating in the airways, critically interferes with the effectiveness of pulmonary gene delivery. To overcome this challenge, nanoparticulate ternary gene-polymer complexes were encapsulated in inhalable dry microparticles containing mannitol. When applied on a layer of artificial sputum, which comprised major components of CF sputum such as DNA and mucin, mannitol microparticles rapidly dissolved in it and enhanced transport of nanoparticles across the sputum layer. Despite the improvement of nanoparticle transport in the artificial sputum, the gene-polymer complex passing the sputum did not show gene transfection because of the significant inactivation by DNA and, to a lesser extent, mucin. Particle size measurement suggested that aggregation of the gene transfer agents was mainly responsible for the activity loss. These results indicate that the delivery of gene transfer agent across CF sputum depended not only on the ability to penetrate the sputum but also on preservation of the activity during and/or after the transport. (C) 2011 Elsevier B.V. All rights reserved.
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