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Drug delivery technology predicted to allow safer and more effective use of steroids in the treatment of rheumatoid arthritis

Posted on: 08 Apr 04
Drug delivery technology predicted to allow safer and more effective use of steroids in the treatment of rheumatoid arthritis

Summary

DailyUpdates 8th April: An estimated 5 million individuals suffer from rheumatoid arthritis in the Western world. Corticosteroids are the most dramatically effective short-term anti-inflammatory drugs; however, their clinical benefit for rheumatoid arthritis often diminishes with time. This, the severe rebounds observed following the withdrawal of corticosteroids, and long-term systemic side effects associated with corticosteroids limits their use in the treatment of rheumatoid arthritis. Rese

DailyUpdates 8th April: An estimated 5 million individuals suffer from rheumatoid arthritis in the Western world.  Corticosteroids are the most dramatically effective short-term anti-inflammatory drugs; however, their clinical benefit for rheumatoid arthritis often diminishes with time. This, the severe rebounds observed following the withdrawal of corticosteroids, and long-term systemic side effects associated with corticosteroids limits their use in the treatment of rheumatoid arthritis.  Researchers have now shown that encapsulating steroids in liposomes results in their selective delivery to diseased joints.  This has been shown to facilitate less frequent dosing and may also increase efficacy and reduce side-effects.


Rheumatoid arthritis is one of the more common autoimmune diseases along with multiple sclerosis, type I diabetes and Crohn’s disease. Approximately one in five people in the western world suffer from autoimmune diseases and some estimates indicate that 75% of these are women. In total it is predicted that the annual value of the market for drugs used to treat autoimmune disease will soon exceed $20 billion. An estimated 5 million individuals suffer from rheumatoid arthritis, a figure which will increase to 5.7 million by 2010 (for further information on the rheumatoid arthritis market click here).


Corticosteroids are the most dramatically effective short-term anti-inflammatory drugs; however, their clinical benefit for RA often diminishes with time. Corticosteroids do not predictably prevent the progression of joint destruction, although a recent report suggested that they might slow erosions. Furthermore, severe rebound follows the withdrawal of corticosteroids in active disease. Because of their long-term systemic side effects, corticosteroids are usually given only after a careful and prolonged trial of less hazardous drugs.


Future directions for the development of rheumatoid arthritis therapeutics are ever focusing on disease modifying drug classes (LeadDiscovery's Rheumatoid arthritis: Emerging drug discovery targets and therapeutic candidates is recommended for readers requiring a full overview of DMARDs click here).  An alternate strategy however is the utilization of evolving drug delivery technology to target classic therapeutics such as the steroids to arthritic joints.


In their April Annals of Rheumatological Disease article Metsellaar et al report that liposomal targeting of glucocorticoids to synovial lining cells strongly increases therapeutic benefit in an experimental model of arthritis.

This group from the Utrecht Institute of Pharmaceutical Sciences investigated the effect of a single intravenous treatment with glucocorticoids encapsulated in long-circulating PEG-liposomes on both joint inflammation and cartilage destruction and investigated the phenomenon of selective homing of these liposomes in the inflamed synovium.

 

Mice with collagen type II-induced arthritis were intravenously treated with liposomal and free prednisolone phosphate following the onset of disease.  Treatment with 10 mg/kg liposomal prednisolone phosphate resulted in a strong and lasting resolution of joint inflammation. 10 mg/kg free prednisolone phosphate only became slightly effective after repeated daily injections. Although joint inflammation recurred 1 week after treatment with liposomal prednisolone phosphate, knee joint sections prepared at this time indicated that the cartilage damage was still reduced. Histochemical evaluation revealed that liposomes concentrated in the synovial lining of diseased joints while unaffected joints did not take up liposomes.

 

This important study suggests that liposomal technology may target steroid to inflamed joints resulting in fewer administrations to produce greater efficacy with reduced side-affects in patients with rheumatoid arthritis.

Source DailyUpdates 8th April; for a full abstract of the original papers see  Ann Rheum Dis. 2004 Apr;63(4):348-353


Recommended further reading:



Of additional interest to the rheumatologist, Savient Pharmaceuticals today announced that it has initiated a Phase II clinical study of Puricase, a polyethylene glycol conjugate of uricase (urate oxidase), in the treatment of severe, refractory gout. For details of this release click here


 

In this edition of DailyUpdates, LeadDiscovery also highlights the effects of cigarette smoke and neutrophil elastase on epithelial chemokine release...a mechanistic approach to the design of COX-1 selective agents... the role of 11beta-Hydroxysteroid Dehydrogenase Type 1 in metabolic disease...and much more.

LeadDiscovery

Last updated on: 27/08/2010 11:40:18

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