Enhanced anti-inflammatory activity of a liposomal intercellular adhesion molecule-1 antisense oligodeoxynucleotide in an acute model of contact hypersensitivity

The anti-inflammatory activity of free and liposome-encapsulated oligonucle otide targeted against intercellular adhesion molecule-1 mRNA was investiga ted in a delayed type hypersensitivity model of acute inflammation in mice. Contact hypersensitivity reactions to 2,4-dinitrofluorobenzene were monito red by measuring ear thickness and cellular infiltration, both of which wer e observed to be maximal 24 h after ear challenge. A murine-specific phosph orothioate oligodeoxynucleotide and various control sequences were each pas sively encapsulated into 100-nm diameter large unilamellar vesicles compose d of egg phosphatidylcholine and cholesterol. All formulations were adminis tered as a single-bolus injection into the tail vein similar to 15 min afte r initiating ear inflammation. Oligodeoxynucleotide dose was varied from 5 to 50 mg/kg and the extent of inflammation was assessed 24 h later. Mice tr eated with free oligonucleotide, empty vesicles, or encapsulated control se quences showed no measurable effect on ear swelling or cellular infiltratio n compared with untreated controls. However, mice that received the active sequence encapsulated in lipid vesicles exhibited near baseline levels of e ar thickness and leukocyte infiltration, similar to that observed in mice t reated with a topical corticosteroid. These data demonstrate the utility of liposome-encapsulated intercellular adhesion molecule-1 antisense oligonuc leotide as a novel anti-inflammatory therapeutic.