Zhang Lan, Yan Min, Chen Kun, Tian Qikang, Song Junying, Zhang Zijuan, Xie Zhishen, Yuan Yong, Jia Yaquan, Zhu Xin, Zhang Zhenqiang, Wu Xiangxiang, Zeng Huahui
Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Pharmacy College, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Pharmaceutics. 2020 Feb 26;12(3):202. doi: 10.3390/pharmaceutics12030202.
A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (> 5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo.
通过将雷公藤甲素（TP）与羧甲基壳聚糖（CMCS）偶联，制备了一种用于递送雷公藤甲素的新平台。与天然雷公藤甲素相比，含有约5 wt%雷公藤甲素的雷公藤甲素偶联物（TP-CMCS）表现出优异的水溶性（>5 mg/mL）。体外实验结果表明，TP-CMCS可以分别减轻TP对RAW264.7细胞的抑制作用和凋亡。与TP组相比，TP-CMCS可以有效减轻TP的毒性损伤并降低小鼠的死亡率（p<0.05）。TP-CMCS对肝脏（AST和ALT）和肾脏（BUN和CRE）没有造成太大损伤（p<0.05）。给药后，TP-CMCS组和TP组中IL-6、IL-1β和TNF-α水平降低，关节炎消肿百分比显著增加，骨侵蚀程度明显降低。我们的结果表明，TP-CMCS是治疗类风湿性关节炎的一种有用载体，它提高了游离TP的水溶性并降低了体外和体内的药物毒性。
