edoc

Efficient topical delivery of plasmid DNA to lung in vivo mediated by putative triggered, PEGylated pDNA nanoparticles

Aissaoui, Abderrahim and Chami, Mohamed and Hussein, Mahamoud and Miller, Andrew D.. (2011) Efficient topical delivery of plasmid DNA to lung in vivo mediated by putative triggered, PEGylated pDNA nanoparticles. Journal of Controlled Release, 154 (3). pp. 275-284.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/88848/

Downloads: Statistics Overview

Abstract

Non-viral vectors are considered safer than viral vectors and show clinical potential, but remain less efficient in terms of DNA delivery. Here we report how cationic liposomes, prepared from new cationic lipid, N',N',-dioctadecyl-N-4,8-diaza-10-aminodecanoylglycine amide (DODAG) and neutral lipid dioleoyl-L-α-phos-phatidylethanolamine (DOPE), can be formulated with plasmid DNA (pDNA) in the presence of stabilizer cholesteryl-oxycarbonylpolyethlylene glycol(4600) (PEG(4600)-Chol) giving PEGylated pDNA nanoparticles (pDNA-ABC nanoparticles) that are proposed to be half-life triggered nanoparticles. In particular, the PEGylated pDNA nanoparticle formulation DODAG/DOPE/PEG(4600)-Chol (43:43:14, m/m/m)-pDNA (total lipid/pDNA ratio 4:1 w/w) (pTRANSplus nanoparticles) is shown to mediate efficient transfection of murine lung tissue in vivo. Levels of transfection compare well with the results of polyethylenimine (PEI) mediated pDNA transfection in vivo and even of adenovirus mediated transduction. Cryo-EM imaging indicates that pTRANSplus formulations are somewhat heterogeneous but do consist primarily of bilammellar lipoplex nanoparticles with a few multilammellar nanoparticle aggregates. Lung histology confirms that pTRANSplus mediated transfection in vivo targets substantially the epithelial cells of bronchii and bronchioli airway passages. The pTRANSplus nanoparticle system is a useful new starting point for nucleic acid therapeutic strategies to counter lung disorders such as viral infection and possibly cystic fibrosis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Engel)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > BioEM Lab (Chami)
UniBasel Contributors:Chami, Mohamed
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0168-3659
e-ISSN:1873-4995
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:19 Jul 2022 11:14
Deposited On:19 Jul 2022 11:14

Repository Staff Only: item control page