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New Hope For Arthritis Patients: Fighting Inflammation With Targeted Liposomal Therapy

Date:
March 29, 2006
Source:
John Wiley & Sons, Inc.
Summary:
The results of a recent study indicate the promise of targeted liposomal therapy for rheumatoid arthritis patients.

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.

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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 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 injected with an empty liposomes. To allow examination of liposome interactions with blood vessel walls in living animals, researchers used a mouse dorsal skin flap window model and distinguished RGD-PEG liposomes by fluorescent labels.

One hour after injection of the liposomes, which was performed only four hours after the induction of the inflammation, researchers observed strong binding of the RGD-PEG liposomes to the blood vessel wall at the site of the inflammation. Besides their rapid attack on VEC activity, the binding of RGD-PEG liposomes to inflamed sites was three-fold higher than that of the liposomes without the peptide.

Disease activity and its toll were monitored among the rats with AIA. Arthritis severity was scored by grading each paw from 0 to 4, based on redness, swelling, and joint immobility, with a maximum possible score of 16 per animal. Rats treated with DEXP-containing RGD-PEG liposomes showed the lowest overall scores, the strongest anti-inflammatory effects, and delayed disease progression.

This study demonstrates the potential of corticosteroid-carrying, VEC-binding RGD liposomes to quickly relieve inflammation and significantly reduce its ravages. "Using these liposomes to deliver DEXP to VECs at sites of arthritis involvement proved very efficacious in rat AIA, indicating promise for the treatment of rheumatoid arthritis," note the study's leading authors, Gert Storm, Ph.D. and Gerben Koning, Ph.D. "Future research will focus more precisely on the mechanisms involved and may also explore delivery of other anti-inflammatory compounds by the RGD-targeted liposomes."

Article: "Targeting of Angiogenic Endothelial Cells at Sites of Inflammation by Dexamethasone Phosphate-Containing RGD Peptide Liposomes Inhibits Experimental Arthritis," Gerben A. Koning, Raymond M. Schiffelers, Marca H. M. Wauben, Robber J. Kok, Enrico Mastrobattista, Grietje Molema, Timo L. M. ten Hagen, and Gert Storm, Arthritis & Rheumatism, April 2006, 54:4, pp. 1198-1208.


Story Source:

The above story is based on materials provided by John Wiley & Sons, Inc.. Note: Materials may be edited for content and length.


Cite This Page:

John Wiley & Sons, Inc.. "New Hope For Arthritis Patients: Fighting Inflammation With Targeted Liposomal Therapy." ScienceDaily. ScienceDaily, 29 March 2006. <www.sciencedaily.com/releases/2006/03/060329083600.htm>.
John Wiley & Sons, Inc.. (2006, March 29). New Hope For Arthritis Patients: Fighting Inflammation With Targeted Liposomal Therapy. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2006/03/060329083600.htm
John Wiley & Sons, Inc.. "New Hope For Arthritis Patients: Fighting Inflammation With Targeted Liposomal Therapy." ScienceDaily. www.sciencedaily.com/releases/2006/03/060329083600.htm (accessed November 28, 2014).

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