Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
Nonviral siRNA delivery to the lung: Investigation of PEG-PEI polyplexes and their in vivo performance.
Mol. Pharm. 6, 1246-1260 (2009)
This study describes the physicobiological characterization of PEI- and PEG-PEI polyplexes containing partially 2'-OMe modified 25/27mer dicer substrate siRNAs (DsiRNAs) and their in vivo behavior regarding biodistribution and systemic bioavailability after pulmonary application as well as their ability to knock down gene expression in the lung. Biophysical characterization included circular dichroism of siRNA in polyplexes, condensation efficiency of polymers and in vitro stability. After in vivo application, biodistibution and kinetics of radiolabeled polyplexes, were quantified and recorded over time in three-dimensional SPECT images and by end point scintillation counting. The influence on lung tissue and on the humoral and cellular immunosystem was investigated, and finally knockdown of endogenous gene expression in the lung was determined qualitatively. While all of the polymers used in our study were proven to effectively condense siRNA, stability of the complexes depended on the PEG grafting degree. Interestingly, PEI 25 kDa, which showed the least interaction with mucin or surfactant in vitro, performed poorly in vivo. Our nuclear imaging approach enabled us to follow biodistribution of the instilled nanocarriers over time and indicated that PEGylated nanocarriers are more suitable for lung application. While moderate proinflammatory effects were attributed to PE125k-PEG(2k)(10) nanocarriers, none of the treatments caused histological abnormalities. Our preliminary in vivo knockdown experiment suggests that PEG-PEI/siRNA complexes are promising nanomedicines for pulmonary siRNA delivery. These results encouraged us to further investigate possible adverse effects and to quantify in vivo gene silencing in the lung after intratracheal instillation of PEG-PEI/siRNA complexes.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
siRNA; lung; nonviral vectors; SPECT; PEI; lung surfactant; mucin; intratracheal; GIFP; knockdown; circular-dichroism; ultrafine particles; block-copolymers; rna interference; epithelial-cells; gene delivery; oligonucleotides; complexes; cytokine; glycol)
ISSN (print) / ISBN
1543-8384
e-ISSN
1543-8392
Journal
Molecular Pharmaceutics
Quellenangaben
Volume: 6,
Issue: 4,
Pages: 1246-1260
Publisher
American Chemical Society (ACS)
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Lung Health and Immunity (LHI)