| Liposomal targeting of glucocorticoids to the inflamed synovium inhibits cartilage matrix destruction during murine antigen-induced arthritis. | |
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MedLine Citation:
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PMID: 21382458 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Encapsulation of glucocorticoids into long-circulating liposomes provides targeting of these drugs to the inflamed synovium in experimental arthritis and thereby strongly improves their therapeutic index. The goal of this study was to evaluate the effect and mechanisms of intravenous liposomal delivery of prednisolone phosphate (Lip-PLP) on protease mediated cartilage destruction during murine antigen-induced arthritis (AIA). Mice treated with a single injection of Lip-PLP showed a pronounced suppression of synovial immune cell infiltration compared to control, PBS-treated mice. Liposomal PLP also significantly suppressed interleukin 1β (3.6 fold) in the synovium, but not in the blood serum. Furthermore, expression of the proteases MMP-3, -9, -13 and -14 and ADAMTS-4 and -5 was suppressed by Lip-PLP in the synovium, but not within the articular cartilage of the femur and tibia, demonstrating the specific action of Lip-PLP on the synovium. Lip-PLP is phagocytosed by macrophages in vitro and suppresses their expression of IL-1β and MMP's after LPS activation. Moreover, Lip-PLP suppresses destruction of the cartilage matrix during AIA by active MMP's and ADAMTS, as assessed by immunostaining of their respective neoepitopes VDIPEN and NITEGE in various cartilage layers of the knee joint. Conclusion: Liposomal delivery of glucocorticoids protects against cartilage matrix destruction during experimental arthritis by inhibiting protease expression and activity in the inflamed synovium. |
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Authors:
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W Hofkens; G Storm; W B van den Berg; P L van Lent |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-4 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: - ISSN: 1873-3476 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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