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作 者:Yawei Du Chao Li Yu Zhang Wei Xiong Fei Wang Juan Wang Yingze Zhang Lianfu Deng Xinsong Li Wei Chen Wenguo Cui
机构地区:[1]Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,197 Rujin 2nd Road,Shanghai 200025,China [2]Department of Orthopaedic Surgery,the Third Hospital of Hebei Medical University,No.139 Ziqiang Road,Shijiazhuang 050051,China [3]School of Chemistry and Chemical Engineering,Southeast University,2 Southeast University Road,Nanjing 21189,China
出 处:《Research》2023年第3期187-203,共17页研究(英文)
基 金:the National Key Research and Development Program of China(2020YFA0908200);National Natural Science Foundation of China(91949203 and 22105127);Shanghai Municipal Health Commission(202140128);Shanghai Pujiang Program(21PJD045);Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT320001);Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906);GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine.
摘 要:In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.
关 键 词:activation drugs preparing
分 类 号:TP3[自动化与计算机技术—计算机科学与技术]
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