Liposomal targeting of glucocorticoids to the inflamed synovium inhibits cartilage matrix destruction during murine antigen-induced arthritis

被引：41

作者：

Hofkens, W. ^{[1
]}

Storm, G. ^{[2
]}

van den Berg, W. B. ^{[1
]}

van Lent, P. L. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Dept Rheumatol, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[2] Univ Utrecht, Dept Pharmaceut, UIPS, Utrecht, Netherlands

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2011年 / 416卷 / 02期

关键词：

Liposomes; Animal model; Rheumatoid arthritis; Glucocorticoid; Cartilage destruction; INTERLEUKIN-1 RECEPTOR ANTAGONIST; COLLAGEN-INDUCED ARTHRITIS; ARTICULAR-CARTILAGE; JOINT INFLAMMATION; LINING CELLS; DEXAMETHASONE PHOSPHATE; II ARTHRITIS; EXPRESSION; AGGRECANASE; FIBROBLASTS;

D O I：

10.1016/j.ijpharm.2011.02.060

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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 (ALA). 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 1 beta (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-1 beta and MMPs after LPS activation. Moreover, Lip-PLP suppresses destruction of the cartilage matrix during AM mediated by active MMPs 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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：486 / 492

页数：7

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