1. Novel Carboxylated Chitosan-Based Triptolide Conjugate for the Treatment of Rheumatoid Arthritis
- Author
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Yuan Yong, Lan Zhang, Junying Song, Xiangxiang Wu, Yan Min, Huahui Zeng, Chen Kun, Xin Zhu, Qikang Tian, Xie Zhishen, Yaquan Jia, Zhenqiang Zhang, and Zhang Zijuan
- Subjects
Pharmaceutical Science ,Arthritis ,lcsh:RS1-441 ,Pharmacology ,01 natural sciences ,Article ,Chitosan ,lcsh:Pharmacy and materia medica ,carboxylmethyl chitosan ,03 medical and health sciences ,chemistry.chemical_compound ,In vivo ,medicine ,030304 developmental biology ,0303 health sciences ,Kidney ,water solubility ,010405 organic chemistry ,drug carrier system ,toxicity ,Triptolide ,medicine.disease ,In vitro ,0104 chemical sciences ,medicine.anatomical_structure ,chemistry ,Apoptosis ,triptolide ,Toxicity - Abstract
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&beta, and TNF-&alpha, 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.
- Published
- 2020
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