Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment  

作　　者：Ruijie Chen Yuan-Yuan Zhai Lining Sun Zeqing Wang Xing Xia Qing Yao Longfa Kou 

机构地区：[1]Department of Pharmacy,the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou 325027,China [2]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第2期268-283,共16页亚洲药物制剂科学（英文）

基　　金：inancially supported by the National Natural Science Foundation of China (81903551);Zhejiang Province Natural Science Foundation (LQ19H300001);Excellent Young Scientist Training Program fund from Wenzhou Medical University

摘　　要：Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells.Recent studies showed that Signal Transducer and Activator of Transcription 3(STAT3),which plays an important role in cell survival,proliferation,differentiation,angiogenesis,and immune responses,is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions.In addition,STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production,thereby exacerbating the condition of psoriasis.Alantolactone(ALT)is a sesquiterpene lactone compound that could selectively suppress STAT3 activation,but its effectiveness and application in psoriasis treatment have not been determined.In this study,we developed ALT loaded chitosan/hyaluronic acid nanoparticles(CHALT),and investigated its therapeutic potential for psoriasis therapy.CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrialmembrane potential,and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line.In an Imiquimod(IMQ)-induced psoriasis model,the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis.In addition,it was found that CHALT restricted the recruitment of immune cells.These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

关 键 词：PSORIASIS ALANTOLACTONE STAT3 CHITOSAN NANOPARTICLE 

分 类 号：R943[医药卫生—药剂学]