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  • Title: Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes.
    Author: Metselaar JM, Wauben MH, Wagenaar-Hilbers JP, Boerman OC, Storm G.
    Journal: Arthritis Rheum; 2003 Jul; 48(7):2059-66. PubMed ID: 12847701.
    Abstract:
    OBJECTIVE: To increase the therapeutic activity of glucocorticoids in experimental arthritis by encapsulation in long-circulating polyethylene glycol liposomes, which have shown the ability to preferentially accumulate in inflamed joints after intravenous administration. METHODS: Rats with adjuvant-induced arthritis (AIA) were treated intravenously with liposomal and free prednisolone phosphate (PLP) a few days after the first signs of disease. The effect on paw inflammation scores during the weeks after treatment was evaluated. Liposome biodistribution and joint localization were investigated by labeling the preparation with radioactive (111)In-oxine. By studying PLP encapsulated in other types of liposomes, which show a distinctive tissue distribution pattern and reduced accumulation in inflamed joints, the importance of targeted delivery to inflamed joints for achieving an increased therapeutic effect was illustrated. RESULTS: Liposomal PLP proved to be highly effective in the rat AIA model. A single injection of 10 mg/kg resulted in complete remission of the inflammatory response for almost a week. In contrast, the same dose of unencapsulated PLP did not reduce inflammation, and only a slight effect was observed after repeated daily injections. Evidence was found that preferential glucocorticoid delivery to the inflamed joint was the key factor explaining the observed strong therapeutic benefit obtained with the liposomal preparation, while other possible mechanisms, such as splenic accumulation or prolonged release of prednisolone in the circulation, were excluded. CONCLUSION: Targeted delivery using long-circulating liposomes is a promising, novel means to successfully intervene in arthritis with glucocorticoid therapy.
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