Article

Novel cationic liposome formulation for the delivery of an oligonucleotide decoy to NF-kappaB into activated macrophages.

Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Naples, Italy.
European Journal of Pharmaceutics and Biopharmaceutics (impact factor: 4.27). 04/2008; 70(1):7-18. DOI:10.1016/j.ejpb.2008.03.012 pp.7-18
Source: PubMed

ABSTRACT Nuclear factor-kappaB (NF-kappaB) is involved in several pathological processes, such as inflammation. Pro-inflammatory genes expression can be down-regulated by using an oligonucleotide (ODN) decoy to NF-kappaB. Cationic liposomes are largely used to improve ODN uptake into cells, although a higher transfection efficiency and a lower toxicity are required to use them in therapy. In this work, we investigated the potential of a novel liposome formulation, based on the recently synthesised cationic lipid (2,3-didodecyloxypropyl) (2-hydroxyethyl) dimethylammonium bromide (DE), as the delivery system for a double stranded ODN decoy to NF-kappaB. Liposomes composed of DE or DE mixed with 1,2-dioleyl-sn-glycero-3-phosphoethanolamine or cholesterol as helper lipids were complexed with ODN at different +/- charge ratios. In vitro uptake and the effect of ODN, naked or complexed with DE-containing liposomes, were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages. The use of helper lipids increased liposome physical stability up to 1 year at 4 degrees C. ODN complexed with DE/cholesterol liposomes, at the +/- charge ratio of 8, showed a limited cytotoxicity and the highest inhibition of nitrite production, inducible nitric oxide synthase protein expression and NF-kappaB/DNA binding activity. Confocal microscopy confirmed a high ODN cell uptake obtained with DE/cholesterol liposomes at the highest +/- charge ratio.

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Keywords

+/- charge ratio
 
4 degrees C. ODN complexed
 
Cationic liposomes
 
Confocal microscopy
 
DE mixed
 
DE-containing liposomes
 
DE/cholesterol liposomes
 
different +/- charge ratios
 
higher transfection efficiency
 
highest +/- charge ratio
 
lipopolysaccharide-stimulated RAW 264.7 macrophages
 
liposome physical stability
 
lower toxicity
 
NF-kappaB/DNA binding activity
 
novel liposome formulation
 
Nuclear factor-kappaB
 
ODN cell uptake
 
pathological processes
 
Pro-inflammatory genes expression
 
synthesised cationic lipid