Document Detail


Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents.
MedLine Citation:
PMID:  23614789     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Receptor-targeted nanocomplexes are nonviral vectors developed for gene delivery to the airway epithelium for the treatment of pulmonary disease associated with cystic fibrosis. The present study aimed to optimize the delivery of the nanocomplex by nebulization, and to monitor the in vivo deposition of radiolabeled vector in the airways of a large animal model by γ-camera scintigraphy. Large White weaner pigs were nebulized with nanocomplexes mixed with technetium-99m radiopharmaceuticals. The aerosol deposition scans suggested that the nebulized radiovectors were deposited mainly in the trachea-main bronchi and in the midregion of the lungs. The plasmid biodistribution, assessed by real-time PCR, correlated with the scintigraphy images. The highest plasmid copy numbers were found in the bronchial areas and in the tissues proximal to the main bronchi bifurcation. Immunohistochemistry detected transgene expression in the tracheal and bronchial ciliated epithelium. Histological analysis of lung tissue showed no evidence of inflammation, and no increase in inflammatory cytokines or inflammatory cells was detected in the bronchoalveolar lavage. The deposition of nebulized nanocomplexes coassociated with technetium-99m can be monitored by nuclear medicine techniques. The use of a noninvasive strategy to follow the delivery of the vector could improve the clinical management of patients undergoing cystic fibrosis gene therapy.
Authors:
Maria D I Manunta; Robin J McAnulty; Amy McDowell; Jing Jin; Deborah Ridout; John Fleming; Stephen E Bottoms; Livia Tossici-Bolt; Geoffrey J Laurent; Lorenzo Biassoni; Christopher O'Callaghan; Stephen L Hart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  49     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-02     Completed Date:  2013-10-25     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  471-80     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cystic Fibrosis / radionuclide imaging
Female
Gene Transfer Techniques*
Genetic Therapy
Humans
Injections, Intravenous
Male
Molecular Imaging / methods*
Nanoconjugates / administration & dosage,  chemistry
Nebulizers and Vaporizers
Plasmids
Radiopharmaceuticals / administration & dosage,  pharmacokinetics*
Respiratory Mucosa / radionuclide imaging*,  ultrastructure
Respiratory System / radionuclide imaging*,  ultrastructure
Swine
Technetium / administration & dosage,  pharmacokinetics*
Grant Support
ID/Acronym/Agency:
G1000440//Medical Research Council
Chemical
Reg. No./Substance:
0/Nanoconjugates; 0/Radiopharmaceuticals; 7440-26-8/Technetium
Comments/Corrections

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