Novel Carboxylated Chitosan-Based Triptolide Conjugate for the Treatment of Rheumatoid Arthritis

• Main Authors: Lan Zhang (Author), Min Yan (Author), Kun Chen (Author), Qikang Tian (Author), Junying Song (Author), Zijuan Zhang (Author), Zhishen Xie (Author), Yong Yuan (Author), Yaquan Jia (Author), Xin Zhu (Author), Zhenqiang Zhang (Author), Xiangxiang Wu (Author), Huahui Zeng (Author)
• Format: Book
• Published: MDPI AG, 2020-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-1&#946;, and TNF-&#945; 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.

Item Description

1999-4923
10.3390/pharmaceutics12030202