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以炎症部位的成纤维样滑膜细胞为靶点,用肽靶向脂质体治疗可抑制实验性关节炎。

Targeting fibroblast-like synovial cells at sites of inflammation with peptide targeted liposomes results in inhibition of experimental arthritis.

机构信息

Department of Rheumatology, Westmead Hospital, Sydney, Australia.

Department of Rheumatology, Westmead Hospital, Sydney, Australia.

出版信息

Clin Immunol. 2014 Mar;151(1):43-54. doi: 10.1016/j.clim.2014.01.005. Epub 2014 Jan 16.

Abstract

In this study we examined a synovium-specific targeted liposomal drug delivery system for its ability to localize and release its drug cargo to inflamed joints. Targeted liposomes were tested in vitro for binding to synovial fibroblast like (FLS) and endothelial cells using flow cytometry and in vivo for localization to joints using a rat model of adjuvant induced arthritis (AIA). Targeted liposomes were then loaded with anti-arthritic medications and examined for clinical efficacy in AIA. Targeted liposomes specifically bound to rabbit FLS and human FLS and showed a 7-10 fold increase in vivo localization in affected joints compared to unaffected joints. Histological sections from rats treated with prednisone and a new immunosuppressive peptide CP showed minimal inflammation. This report substantiates the ability of the novel FLS sequence to target liposomal drug delivery and offers an alternative therapeutic approach for the treatment of arthritis.

摘要

在这项研究中,我们研究了一种滑膜特异性靶向脂质体药物递送系统,以评估其将药物递送到炎症关节的能力。使用流式细胞术检测靶向脂质体与滑膜成纤维样(FLS)细胞和内皮细胞的结合能力,并使用佐剂诱导关节炎(AIA)大鼠模型检测其在关节中的定位。然后将靶向脂质体加载抗关节炎药物,并在 AIA 中检测其临床疗效。靶向脂质体特异性地与兔 FLS 和人 FLS 结合,并在体内与未受影响的关节相比,在受影响的关节中的定位增加了 7-10 倍。用泼尼松和新型免疫抑制肽 CP 治疗的大鼠的组织学切片显示出最小的炎症。本报告证实了新型 FLS 序列靶向脂质体药物递送的能力,并为关节炎的治疗提供了一种替代的治疗方法。

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