Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Control Release. 2011 Jun 30;152(3):363-9. doi: 10.1016/j.jconrel.2011.03.001. Epub 2011 Mar 17.
The objective of this study was to determine the effect of systemic delivery of prednisolone phosphate (PLP) encapsulated within long circulating 'stealth' liposomes on bone erosion and osteoclast activity during experimental antigen-induced arthritis (AIA). Liposomal PLP strongly suppressed knee joint swelling, synovial infiltrate and bone erosion in antigen-induced arthritis. The number of active osteoclasts was not only suppressed in bone lesions near inflamed synovium, but also within the trabecular bone of the tibia, suggesting a systemic suppression of osteoclast activation. Furthermore, liposomal PLP directly blocked osteoclast differentiation and bone resorption in vitro while it also suppressed expression of osteoclast differentiation factors M-CSF and RANKL in the synovium. Targeting studies showed that liposomes are most efficiently phagocytosed by macrophages and early precursors of osteoclasts in the bone marrow rather than by mature osteoclasts, indicating a possible inhibition of osteoclast differentiation from an early stage.
Liposomal glucocorticoid delivery rather than free PLP offers a more efficacious way to inhibit both inflammation and bone erosion in rheumatoid arthritis.
本研究旨在确定在实验性抗原诱导关节炎（AIA）期间，全身给予包封于长循环“隐形”脂质体中的磷酸泼尼松龙（PLP）对骨侵蚀和破骨细胞活性的影响。脂质体 PLP 强烈抑制了抗原诱导关节炎中的膝关节肿胀、滑膜浸润和骨侵蚀。不仅在炎症性滑膜附近的骨病变中，而且在胫骨的小梁骨中，活性破骨细胞的数量均受到抑制，这表明破骨细胞激活受到全身性抑制。此外，脂质体 PLP 不仅在体外直接阻断破骨细胞分化和骨吸收，而且还抑制了滑膜中破骨细胞分化因子 M-CSF 和 RANKL 的表达。靶向研究表明，脂质体最有效地被巨噬细胞和骨髓中破骨细胞的早期前体细胞吞噬，而不是被成熟的破骨细胞吞噬，这表明可能从早期阶段抑制破骨细胞分化。
与游离 PLP 相比，脂质体糖皮质激素给药提供了一种更有效的抑制类风湿关节炎中炎症和骨侵蚀的方法。
