Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation

作     者：Yi Yang Makhloufi Zoulikha Qingqing Xiao Feifei Huang Qi Jiang Xiaotong Li Zhenfeng Wu Wei He Yi Yang;Makhloufi Zoulikha;Qingqing Xiao;Feifei Huang;Qi Jiang;Xiaotong Li;Zhenfeng Wu;Wei He

作者机构：Shanghai Skin Disease HospitalTongji University School of MedicineShanghai 200443China School of PharmacyChina Pharmaceutical UniversityNanjing 2111198China Department of Traditional Chinese Medicine Processing and PreparationNanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Modern Preparation of TCMMinistry of EducationJiangxi University of Chinese MedicineNanchang 330004China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报(英文版))

年 卷 期：2023年第13卷第11期

页      面：4607-4620页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,China (Nos.81872823,82073782 and 82241002) the Shanghai Science and Technology Committee,China (No.19430741500) the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine,China (zdsys202103) 

主　　题：Codelivery Nanocrystals Superoxide dismutase Indomethacin Pulmonary endothelium Inflammation Acute lung injury 

摘      要：Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium ***,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vectorof rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial *** codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%*** and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine ***,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating *** vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial *** vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the *** conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung *** study offers a promising approach to combat pulmonary endothelium-associated diseases.