Vascular endothelial cells (VECs) form the walls of blood vessels and play a critical role in inflammation. In rheumatoid arthritis (RA), VECs interact with cytokines, proteins that regulate immune response, and allow inflammation to persist, escalate, and progressively damage tissue, and joints. Recognized as potent inflammation inhibitors, corticosteroids work to control the expression of cytokines, adhesion molecules and the growth of endothelial cells. The potential of these drugs, however, has been restricted by their considerable toxicity and short half-life.

To study the impact of corticosteroids on VEC activity, researchers in The Netherlands turned to liposomes, microscopic vesicles used to deliver drugs or genetic material directly into a cell. They chose RGD peptide liposomes to deliver a dose of dexamethasone phosphate (DEXP) to VECs at the site of inflammation in rats with experimental arthritis. The results, presented in the April 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), indicate the promise of targeted liposomal therapy for rheumatoid arthritis patients.

RGD peptide was selected for targeting of the liposomes based on its high chemical stability and its high affinity for proteins expressed on angiogenic VECs At sties of inflammation. To create a disease sample, rats with adjuvant-induced arthritis (AIA) and rats or mice were injected with a lipopolysaccharide (LPS)-induced inflammation were used. After disease onset, generally 12 days after the inductions, the rats were randomly divided to receive treatment. One group received a single intravenous injection of 1 milligram of DEXP encapsulated in targeted RGD peptide-exposing polyethylene glycol liposomes (RGD-PEG-L). Another group was injected with the same dosage of DEXP encapsulated in non-targeted PEG liposomes. A control group was
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Contact: Amy Molnar
amolnar@wiley.com
John Wiley & Sons, Inc.
29-Mar-2006

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