PDF(Pubmed)
Abstract：
UNASSIGNED: Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA).
UNASSIGNED: cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model.
UNASSIGNED: cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats.
UNASSIGNED: cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.
UNASSIGNED: cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model.
UNASSIGNED: cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats.
UNASSIGNED: cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.
摘要：
■氟比洛芬酯（FA）是一种非甾体抗炎药，具有良好的镇痛和抗炎作用。然而,它的溶解性差，循环时间短，和脱靶结合概况，严重限制了其临床应用。这里,我们将FA装入精氨酸-甘氨酸-天冬氨酸（RGD）肽（cRGD-FA-SLM）修饰的隐形脂质微球中，并检查了所得平台用于治疗类风湿性关节炎（RA）的治疗潜力。
■cRGD-FA-SLM通过高压均质化制备，使用RAW264.7细胞培养物检查其毒性和巨噬细胞的摄取。进行溶血和肝毒性试验以评估开发平台的安全性，虽然它的药代动力学，生物分布，并在胶原诱导的关节炎大鼠模型中研究治疗效果。
■cRGD-FA-SLM显示出均匀的球形形态和FA的有效包封。开发的平台对正常巨噬细胞无毒，并在体外被脂多糖激活的巨噬细胞选择性内化，而它主要分布在关节炎关节，并显着延长体内循环中的FA。cRGD-FA-SLM还显著降低前列腺素E2的表达,减轻关节水肿和骨侵蚀,在关节炎大鼠中显示出延长的镇痛作用。
■cRGD-FA-SLM表现出良好的炎症靶向能力，延长体内药物循环，提示有望作为靶向治疗RA的抗炎和镇痛剂。
■cRGD-FA-SLM通过高压均质化制备，使用RAW264.7细胞培养物检查其毒性和巨噬细胞的摄取。进行溶血和肝毒性试验以评估开发平台的安全性，虽然它的药代动力学，生物分布，并在胶原诱导的关节炎大鼠模型中研究治疗效果。
■cRGD-FA-SLM显示出均匀的球形形态和FA的有效包封。开发的平台对正常巨噬细胞无毒，并在体外被脂多糖激活的巨噬细胞选择性内化，而它主要分布在关节炎关节，并显着延长体内循环中的FA。cRGD-FA-SLM还显著降低前列腺素E2的表达,减轻关节水肿和骨侵蚀,在关节炎大鼠中显示出延长的镇痛作用。
■cRGD-FA-SLM表现出良好的炎症靶向能力，延长体内药物循环，提示有望作为靶向治疗RA的抗炎和镇痛剂。
