Liposomal codelivery of inflammation inhibitor and collagen protector to the plaque for effective anti-atherosclerosis  

作　　者：Xiaotong Li Jiayi Gu Qingqing Xiao Ying Liu Ping Zhou Lifang Fan Xiulian Zhang Xiang Lu Jun Wu Zhengxia Liu Wei He 

机构地区：[1]School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China [2]Department of Geriatrics,The Second Affiliated Hospital,Nanjing Medical University,Nanjing 210011,China [3]Key Laboratory for Aging&Disease,Nanjing Medical University,Nanjing 210011,China [4]Jiangsu Aosaikang Pharmaceutical Co.,Ltd.,Nanjing 211112,China [5]Department of Respiratory Disease,Baoshan Branch,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200120,China [6]Department of Geriatric Cardiology,Jiangsu Provincial Key Laboratory of Geriatrics,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [7]Department of Geriatrics,The Affiliated Sir Run Run Hospital of Nanjing Medical University,Nanjing 211166,China

出　　处：《Chinese Chemical Letters》2023年第1期239-244,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872823,82073782,81970374);the Shanghai Science and Technology Committee(No.19430741500)。

摘　　要：Plaque plays a central role in atherosclerosis(AS)progression,whereas inflammation and destruction of the plaque microenvironment contribute to plaque advancement.As a result,a therapy regime,which combines anti-inflammation and inhibition-degradation of plaque matrix,appears to be a promising strategy to combat AS.Herein,we report a p H-sensitive liposome co-loading with the anti-inflammatory agent(oridonin,ORD)and plaque-collagen protector(marimastat)for anti-AS therapy.ORD was first conjugated with hyaluronic acid(HA)to target the inflammation contributor,pro-inflammatory macrophages.Then,the conjugate assembled onto the MATT-loaded liposomes.The co-loaded system(150 nm)significantly improved pharmacokinetics over the liposomes without anchoring the conjugate and accumulated effectively in the plaque.The preparation administration allowed efficient anti-AS activities in high-fat diet(HFD)-Apoe-/-mice by decreasing the pro-inflammatory cytokine expression in the serum,lessening the lesion area,alleviating the plaque collagen degradation,promoting macrophage polarization from phenotypic M1 to M2,reducing T helper(Th)17 cells(Th17)/T regulatory cells(Tregs)and Th1/Th2 ratio,etc.Furthermore,the serum determination in AS patients demonstrated high expression of the inflammatory cytokines,indicating our finding may offer a potential guideline for clinical practice.

关 键 词：Atherosclerosis PLAQUE INFLAMMATION COLLAGEN Macrophages CO-DELIVERY Liposomes 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]