纳米载体
药理学
炎症性肠病
化学
药物输送
体内
靶向给药
透明质酸
药品
壳聚糖
细胞毒性
结肠炎
体外
医学
免疫学
生物化学
内科学
生物
生物技术
有机化学
解剖
疾病
作者
Xiaoran Cai,Xiaolei Wang,Muye He,Yan Wang,Minbo Lan,Yuzheng Zhao,Feng Gao
标识
DOI:10.1016/j.ijpharm.2021.120836
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-β-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-β-CD through electrostatic interactions to obtain [email protected]/HA/CS/HP-β-CD nanoparticles ([email protected] 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. [email protected] NPs significantly suppressed secretion of TNF-α, IL-1β 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 [email protected] 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.
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