Novel cationic liposome formulation for the delivery of an oligonucleotide decoy to NF-κB into activated macrophages. Eur J Pharm Biopharm

Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Naples, Italy.
European Journal of Pharmaceutics and Biopharmaceutics (Impact Factor: 3.38). 04/2008; 70(1):7-18. DOI: 10.1016/j.ejpb.2008.03.012
Source: PubMed


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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    • "On the other hand, among different cationic lipids some lipids that are widely used in preparation of cationic liposomes like the DOTAP (11, 12), are permanently positively charged, regardless of the pH (13). This investigation aimed to prepare DOTAP cationic liposomes containing AP1261 as an ODN against protein kinase C-alpha (PKC-α). "
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