Pharmacokinetics, distribution and efficacy of triptolide PLGA microspheres after intra-articular injection in a rat rheumatoid arthritis model

Abstract

1. The UPLC-MS/MS method was established with good precision, accuracy and stability to determine the concentrations of TPL in biological samples, such as heart, liver, spleen, lung, kidney, plasma and joint.

2. After being made into microspheres, TPL can stay in the joint tissue for a long time, further reducing the number of times joint cavity administration, and its sustained release effect was significantly improved compared with the solution dosage form.

3. The pharmacokinetic parameters, such as AUC_(0–t), AUC_(0–∞), T_1/2, T_max, MTR_(0–t), and MTR_(0–∞) of the TPL-PLGA-MS group were significantly increased compared with those of the solution group. The microsphere preparation could significantly slow the release rate of the drug from the joint cavity.

4. TPL-PLGA-MS can significantly reduce the expression of inflammatory factors such as IL-1, IL-6, TNF-α and hs-CRP. TPL-PLGA-MS for articular cavity injection has potential as a new preparation for the treatment of RA.

Keywords:

• Triptolide PLGA microspheres
• distribution
• pharmacokinetics
• intra-articular injection
• efficacy
• rat rheumatoid arthritis model

Author contributions

L.W. performed all experiments and acquisition the data. Y.L. established the UPLC-MS/MS method. L.W. and K.C. participated the animal experiment. L.W. drafted the manuscript.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This work was supported by the projects of basic and frontier projects of Chongqing Science and Technology Bureau [cstc2017jcyjA1119], Science and Technology Research Project of Chongqing Education Commission [KJQN201802801].