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

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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-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.
Funding Information
  • National Natural Science Foundation of China (U1604185, 21601053)
  • Henan Scientific and technological Innovation Talents Project (20HASTIT050)
  • the Scientific and Technological Brainstorm Project of Henan Province (182102410012, 192102310440)
  • the Postdoctoral Fund of China (2018M642761)
  • the Educational Committee Foundation of Henan (20B350003, 19A360021, 19A360002)
  • National Undergraduate Innovation and Entrepreneurship Training Program (201910471013, CXXM[2019]0045)

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