Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis  

作　　者：Xiaobo Zhu Mingde Cao Kejia Li Yau-Tsz Chan Hon-Fai Chan Yi-Wah Mak Hao Yao Jing Sun Michael Tim-Yun Ong Kevin Ki-Wai Ho Chien-Wei Lee Oscar Kuang-Sheng Lee Patrick Shu-Hang Yung Yangzi Jiang 

机构地区：[1]Institute for Tissue Engineering and Regenerative Medicine,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Shatin,Hong Kong Special Administrative Region of China,China [2]School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Shatin,Hong Kong Special Administrative Region of Chin1,China [3]Department of Orthopaedics&Traumatology,Faculty of Medicine,The Chinese University of Hong Kong,Prince of Wales Hospital,Shatin,Hong Kong Special Administrative Region of Chin1,China [4]Center for Neuromusculoskeletal Restorative Medicine,Hong Kong Special Administrative Region of Chin1,China [5]Key Laboratory for Regenerative Medicine,Ministry of Education,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong Special Administrative Region of Chin1,China [6]Department of Orthopaedic Surgery,The First Affiliated Hospital,School of Medicine,Zhejiang University,China

出　　处：《Bioactive Materials》2024年第9期255-272,共18页生物活性材料（英文）

基　　金：supports from all parties during the Covid-19 pandemic;supported by(1)the National Key R&D Program of China(Project No.2019YFA0111900 to YJ),which is financed by the Ministry of Science and Technology of the People’s Republic of China(MOST,China);supported by a grant from the NSFC/RGC Joint Research Scheme sponsored by the Research Grants Council of the Hong Kong Special Administrative Region,China and the National Natural Science Foundation of China(Project No.N_CUHK483/22 to YJ);the Center for Neuromusculoskeletal Restorative Medicine[CNRM at InnoHK,to YJ,HC,PY]by Innovation and Technology Commission(ITC)of Hong Kong SAR,China;the Natural Science Foundation of China(Project No 82302728 to XZ);The Chinese University of Hong Kong.

摘　　要：Osteoarthritis(OA)is a major clinical challenge,and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets.Effective early treatments are urgently needed to prevent OA progression.The excessive amount of transforming growth factorβ(TGFβ)is one of the major causes of synovial fibrosis and subchondral bone sclerosis,and such pathogenic changes in early OA precede cartilage damage.Herein we report a novel strategy of intra-articular sustained-release of pirfenidone(PFD),a clinically-approved TGFβinhibitor,to achieve disease-modifying effects on early OA joints.We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1(as those levels found in patients’synovial fluid).A monthly injection strategy was then designed of using poly lactic-co-glycolic acid(PLGA)microparticles and hyaluronic acid(HA)solution to enable a sustained release of PFD(the“PLGA-PFD+HA”strategy).This strategy effectively regulated OA progression in destabilization of the medial meniscus(DMM)-induced OA mice model,including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA,and reduced synovitis and pain with cartilage preservation effects.This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

关 键 词：TGFβ1 signaling OSTEOARTHRITIS Subchondral bone Pirfenidone DMOAD 

分 类 号：R68[医药卫生—骨科学]