BACKGROUND Targeted delivery to the Rheumatoid arthritis (RA) which is characterized by destruction and degeneration of bones due to chronic inflammation is of great need. RA being a chronic autoimmune disorder might result in severe disability and morbidity. A targeted delivery system is designed to deliver methotrexate (MTX) for RA. METHODS Here, we synthesized folic acid (FA) conjugated hydrophobically modified glycol chitosan (GC) self-assembled nanoparticles (FA-GC-SA) for the targeted delivery of MTX to RA. The FA conjugation and hydrophobic modification of GC by stearic acid (SA) was confirmed by Fourier-transform infrared spectroscopy (FTIR). The FA-GC-SA was exploited for developing targeted nanoparticles encapsulating MTX by the ionic gelation method. The particles were characterized and evaluated for their targeting potential in in vitro cell culture studies. Further their in vivo efficacy in arthritis induced rats using collagen was also evaluated. RESULTS FTIR confirms the successful modification of GC-SA and FA-GC-SA. The FA-GC-SA-MTX of size 153 ± 9 nm were prepared with high encapsulation efficiency of MTX. The FA-GC-SA-MTX size was further confirmed by transmission electron microscopy (TEM). In vitro cell studies revealed the superior efficacy of FA-GC-SA-MTX in cell cytotoxicity. Also, significantly higher cellular uptake of FA functionalized FA-GC-SA-MTX was observed in comparison to non-functionalized GC-SA-MTX attributed to folate receptors (FRs) mediated endocytosis. In vivo results confirms the potential of FA-GC-SA-MTX which reduces reduces the pro-inflammatory cytokines, paw thickness, and arthritis score in collagen induced rats. CONCLUSION The results shows that FRs targeted FA-GC-SA-MTX has superior efficacy in the treatment of RA.

中文翻译：

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叶酸共轭疏水性改性乙二醇壳聚糖纳米粒用于甲氨蝶呤靶向递送类风湿性关节炎

背景技术非常需要靶向递送至特征在于由于慢性炎症引起的骨骼破坏和退化的类风湿性关节炎(RA)。RA 是一种慢性自身免疫性疾病，可能导致严重的残疾和发病率。靶向给药系统旨在为 RA 提供甲氨蝶呤 (MTX)。方法 在这里，我们合成了叶酸 (FA) 共轭疏水改性乙二醇壳聚糖 (GC) 自组装纳米粒子 (FA-GC-SA)，用于将 MTX 靶向递送至 RA。傅里叶变换红外光谱 (FTIR) 证实了硬脂酸 (SA) 对 GC 的 FA 共轭和疏水改性。FA-GC-SA 被用于通过离子凝胶法开发包封 MTX 的靶向纳米粒子。在体外细胞培养研究中对颗粒进行了表征和评估其靶向潜力。此外，还评估了它们在使用胶原蛋白诱导的关节炎大鼠中的体内功效。结果 FTIR 证实了 GC-SA 和 FA-GC-SA 的成功修改。制备了尺寸为 153 ± 9 nm 的 FA-GC-SA-MTX，具有 MTX 的高封装效率。FA-GC-SA-MTX 尺寸通过透射电子显微镜 (TEM) 进一步确认。体外细胞研究揭示了 FA-GC-SA-MTX 在细胞毒性方面的卓越功效。此外，与归因于叶酸受体 (FR) 介导的内吞作用的非功能化 GC-SA-MTX 相比，观察到 FA 功能化 FA-GC-SA-MTX 的细胞摄取显着更高。体内结果证实了 FA-GC-SA-MTX 降低促炎细胞因子的潜力，胶原诱导大鼠的爪子厚度和关节炎评分。结论结果表明，靶向FA-GC-SA-MTX的FRs治疗RA具有较好的疗效。