文献类型：期刊文献

英文题名：Colon-specific delivery of methotrexate using hyaluronic acid modified pH-responsive nanocarrier for the therapy of colitis in mice

作者：Lv, Yingni[1];Ren, Mengjiao[1];Yao, Min[1];Zou, Jiafeng[1];Fang, Siqi[1];Wang, Yanbing[1];Lan, Minbo[2];Zhao, Yuzheng[1,3,4,5,6];Gao, Feng[1,2,3,4,7]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[6]Chinese Acad Med Sci, Res Unit New Tech Live cell Metab Imaging, Beijing 100000, Peoples R China;[7]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：635

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000953024000001)】；

基金：The authors are gratefully the support from National Key Research and Development Program of China (contract No.2019YFA0904800) , National Nature Science Foundation of China (32030065, 31722033, 92049304 to Y.Z.) , Science and Technology Commission of Shanghai Municipality (contract No.10DZ2220500) and The Shanghai Committee of Science and Technology (grant No.11DZ2260600) . Shanghai Frontiers Science Center 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：Inflammatory bowel disease; Methotrexate; Oral nano drug delivery system; pH-sensitive; Colon-specific; Active targeting

摘要：Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of clinical application of MTX, poly (lactic-co-glycolic acid) (PLGA), Eudragits (R) S100 (ES100), chitosan (CS) and hyaluronic acid (HA) were used to structure the MTX-loaded HA-CS/ES100/PLGA nanoparticles (MTX@hCEP). MTX@hCEP had a hydrodynamic particle size of approximately 202.5 nm, narrow size distribution, negative zeta potential (-18.7 mV), and smooth surface morphology. In vitro drug release experiments under simulated gastrointestinal conditions indicated that MTX@hCEP exhibited colonic pH-sensitive drug release properties. The cellular uptake capacity of hCEP nanoparticles was significantly enhanced in RAW 264.7 macrophages. Moreover, we further found that the MTX@hCEP also inhibited the proliferation and the secretion of pro-inflammatory cytokines in the LPS-stimulated macrophages. In vivo im-aging results not only demonstrated that the accumulated in the colon of colitis mice, but also indicated the extended retention time of MTX in the colon. Additionally, MTX@hCEP alleviated inflammatory symptoms via decreasing the activities of myeloperoxidase and pro-inflammatory factors, promoting mucosal repair in vivo. Collectively, these results clearly demonstrated that MTX@hCEP with properties of colon-specific and macro-phages targeting can be exploited as an efficient nanotherapeutic for IBD therapy.