文献类型：期刊文献

英文题名：Colon-targeted delivery of tacrolimus using pH-responsive polymeric nanoparticles for murine colitis therapy

作者：Cai, Xiaoran[1,2];Wang, Xiaolei[2];He, Muye[2];Wang, Yan[2];Lan, Minbo[3];Zhao, Yuzheng[1,4];Gao, Feng[1,2,3]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg Technol, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, Shanghai 200237, Peoples R China

年份：2021

卷号：606

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000692244000003)】；

基金：This work was supported by National Key Research and Development Program of China (contract No.2019YFA0904800) , Technology Commission of Shanghai Municipality (contract No.10DZ2220500) and The Shanghai Committee of Science and Technology (grant No.11DZ2260600) .

语种：英文

外文关键词：Oral nanoparticle delivery system; pH-responsive; Targeted drug delivery; Tacrolimus; Inflammatory bowel diseases

摘要：The present study aimed at constructing an oral nanoparticle delivery system loaded with tacrolimus (FK506) for effective treatment of inflammatory bowel disease. A FK506/HP-beta-CD inclusion compound was prepared by grinding to increase drug solubility. To address the side- effects in non-target organs and systemic toxicity of FK506, pH-responsive Eudragit S100 (ES100) and hyaluronic acid (HA) with high affinity to CD44 receptor were adsorbed onto the surface of chitosan (CS) nanoparticles loaded with FK506/HP-beta-CD through electrostatic interactions to obtain FK506@ES100/HA/CS/HP-13-CD nanoparticles (FK506@EHCh NPs). Caco-2 cells and Raw 264.7 macrophages were used to confirm the lack of cytotoxicity and good uptake ability of the newly generated nanoparticles. FK506@EHCh NPs significantly suppressed secretion of TNF-alpha, IL-1 beta and IL-6 by LPS-activated Raw 264.7 macrophages. A dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) murine model was established to further confirm the colon targeting and in vivo efficacy of oral IR-775@EHCh NPs. Based on the collective results, we conclude that packaging FK506 into active targeting nanocarriers sensitive to pH facilitates concentration of the drug within the sites of intestinal inflammation and improves the drug levels in target tissues, thus avoiding systemic side-effects and improving efficacy. In view of the promising results obtained in this study, the potential of EHCh nanoparticles for drug delivery and targeted treatment of inflammatory bowel disease warrants further investigation.