An intra-articular injectable phospholipids-based gel for the treatment of rheumatoid arthritis  

作　　者：Yuping Yang Shiqin Luo Xiong Peng Ting Zhao Qin He Mengying Wu Wei Zhang Tao Gong Zhirong Zhang 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610064,China [2]Department of Pharmacy,West China Hospital Sichuan University Jintang Hospital,Chengdu 610000,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2023年第1期120-131,共12页亚洲药物制剂科学（英文）

基　　金：financially supported by the National Natural Science Foundation of China (Nos. 82173758, China);Sichuan major science and technology project on biotechnology and medicine (2018SZDZX0018, China)

摘　　要：Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.

关 键 词：Celastrol Rheumatoid arthritis Phospholipids-based controlled release gel Intra-articular drug delivery 

分 类 号：R593.22[医药卫生—内科学]