文献类型：期刊文献

英文题名：XA pH-Responsive and Colitis-Targeted Nanoparticle Loaded with Shikonin for the Oral Treatment of Inflammatory Bowel Disease in Mice

作者：Feng, Juewen[5];Wang, Yanbing[5];Lv, Yingni[5];Fang, Siqi[5];Ren, Mengjiao[5];Yao, Min[1,2,3,5];Lan, Minbo;Zhao, Yuzheng[4];Gao, Feng[4,5]

机构：[1]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Sch Pharm, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[2]Chinese Acad, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[3]Chinese Acad Med Sci, Res Unit New Tech L cell Metab Imaging, Beijing 100050, Peoples R China;[4]East China Univ Sci & Technol, Synthet Biol Interdisciplinary Res Ctr, Sch Pharm & Optogenet, State Key Lab Bioreact Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Sch Pharm, Shanghai 200237, Peoples R China

年份：2022

卷号：19

期号：11

起止页码：4157

外文期刊名：MOLECULAR PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000863256100001)】；

基金：Development Program of China (contract No. 2019YFA0904800) , National Nature Science Foundation of China (32030065, 31722033, 92049304 to Y.Z.) , Shanghai Sailing Program (contract No. 21YF1410300) , Science and Technology Commission of Shanghai Municipality (contract No. 10DZ2220500) and the Shanghai Committee of Science and Technology (grant No. 11DZ2260600) . Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education commission, grant 2021 Sci & Tech 03-28) . Shanghai Municipal Education Commission-Frontier Research Base of Optogenetic Techniques for Cell Metabolism (Y.Z.) , Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019-I2M-5-013 to Y.Z.) , the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：oral; nanoparticle; pH-sensitive; colitis-targeted; shikonin; inflammatory bowel disease

摘要：Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-alpha, IL-6, and IL-1 beta) and anti-inflammatory cytokines (IL-10 and TGF-beta), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.