PT  - JOURNAL ARTICLE
AU  - Fein, David E.
AU  - Bucki, Robert
AU  - Byfield, Fitzroy
AU  - Leszczynska, Katarzyna
AU  - Janmey, Paul A.
AU  - Diamond, Scott L.
TI  - Novel Cationic Lipids with Enhanced Gene Delivery and Antimicrobial Activity
AID  - 10.1124/mol.110.066670
DP  - 2010 Sep 01
TA  - Molecular Pharmacology
PG  - 402--410
VI  - 78
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/78/3/402.short
4100  - http://molpharm.aspetjournals.org/content/78/3/402.full
SO  - Mol Pharmacol2010 Sep 01; 78
AB  - Cationic lipids facilitate plasmid delivery, and some cationic sterol-based compounds have antimicrobial activity because of their amphiphilic character. These dual functions are relevant in the context of local ongoing infection during intrapulmonary gene transfer for cystic fibrosis. The transfection activities of two cationic lipids, dexamethasone spermine (DS) and disubstituted spermine (D2S), were tested as individual components and mixtures in bovine aortic endothelial cells and A549 cells. The results showed a 3- to 7-fold improvement in transgene expression for mixtures of DS with 20 to 40 mol% D2S. D2S and coformulations with DS, dioleoyl phosphatidylethanolamine, and DNA exhibited potent bactericidal activity against Escherichia coli MG1655, Bacillus subtilis, and Pseudomonas aeruginosa PAO1, which was maintained in bronchoalveolar lavage fluid. Complete bacterial killing was demonstrated at ∼5 μM, including gene delivery formulations, with 2 orders of magnitude higher tolerance before eukaryotic membrane disruption (erythrocyte hemolysis). D2S also exhibited lipopolysaccharide (LPS) scavenging activity resulting in significant inhibition of LPS-mediated activation of human neutrophils with 85 and 65% lower interleukin-8 released at 12 and 24 h, respectively. Mixtures of DS and D2S can improve transfection activity over common lipofection reagents, and D2S has strong antimicrobial action suited for the suppression of bacterial-mediated inflammation.