Document Detail

Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents.
MedLine Citation:
PMID:  23614789     Owner:  NLM     Status:  MEDLINE    
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.
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
Related Documents :
2281819 - Immunocytochemical detection of calcitonin gene-related peptide in the postnatal develo...
17645789 - Resequencing pnmt in european hypertensive and normotensive individuals: no common susc...
21949849 - Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-cau...
18209729 - Targeting the murine serotonin transporter: insights into human neurobiology.
15979049 - Endocrine pancreatic tissue plasticity in obese humans is associated with cytoplasmic e...
18591389 - Neuronatin: a new inflammation gene expressed on the aortic endothelium of diabetic mice.
15913539 - Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin d induced...
18241849 - Molecular mechanism of apoptosis and gene expressions in human lymphoma u937 cells trea...
8388539 - Biased t-cell receptor delta element recombination in scid thymocytes.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cystic Fibrosis / radionuclide imaging
Gene Transfer Techniques*
Genetic Therapy
Injections, Intravenous
Molecular Imaging / methods*
Nanoconjugates / administration & dosage,  chemistry
Nebulizers and Vaporizers
Radiopharmaceuticals / administration & dosage,  pharmacokinetics*
Respiratory Mucosa / radionuclide imaging*,  ultrastructure
Respiratory System / radionuclide imaging*,  ultrastructure
Technetium / administration & dosage,  pharmacokinetics*
Grant Support
G1000440//Medical Research Council
Reg. No./Substance:
0/Nanoconjugates; 0/Radiopharmaceuticals; 7440-26-8/Technetium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Modification of a Designed Amphipathic Cell Penetrating Peptide and Its Effect on Solubility, Second...
Next Document:  Arylation of Aldehyde Homoenolates with Aryl Bromides.