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乳铁蛋白介导的巨噬细胞靶向递送及基于广藿香醇的炎症性肠病治疗策略

Lactoferrin-mediated macrophage targeting delivery and patchouli alcohol-based therapeutic strategy for inflammatory bowel diseases.

作者信息

Zhao Yuge, Yang Yuting, Zhang Jiaxin, Wang Rong, Cheng Biyun, Kalambhe Dipika, Wang Yingshu, Gu Zeyun, Chen Dongying, Wang Bing, Huang Yongzhuo

机构信息

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Nanchang University College of Pharmacy, Nanchang 330006, China.

出版信息

Acta Pharm Sin B. 2020 Oct;10(10):1966-1976. doi: 10.1016/j.apsb.2020.07.019. Epub 2020 Aug 5.

DOI:10.1016/j.apsb.2020.07.019
PMID:33163347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7606100/
Abstract

Inflammatory bowel diseases (IBD) are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs. In this study, patchouli alcohol, a main active compound of traditional Chinese herb patchouli, was developed into biomimetic liposomes for macrophage-targeting delivery for IBD treatment. The developed lactoferrin-modified liposomes (LF-lipo) can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy. LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-B pathway. LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1 activation. LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model, evidenced by the reduced disease activity index, the improved colon functions, and the downregulated inflammatory cytokines in the colon. LF-lipo provided an effective and safe macrophage-targeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.

摘要

炎症性肠病（IBD）是无法治愈的慢性复发性胃肠道疾病，目前缺乏安全有效的药物。在本研究中，将传统中药广藿香的主要活性成分广藿香醇开发成用于巨噬细胞靶向递送以治疗IBD的仿生脂质体。所制备的乳铁蛋白修饰脂质体（LF-lipo）可特异性结合活化结肠巨噬细胞上表达的LRP-1，实现细胞靶向抗炎治疗。LF-lipo降低了炎性细胞因子和ROS水平，抑制了MAPK/NF-κB信号通路。LF-lipo还抑制了NLRP3炎性小体的形成及随后的IL-1活化。在DSS诱导的结肠炎小鼠模型中，LF-lipo显示出改善的治疗效果，表现为疾病活动指数降低、结肠功能改善以及结肠中炎性细胞因子下调。LF-lipo为解决IBD治疗中未满足的医疗需求提供了一种有效且安全的巨噬细胞靶向递送及治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/79a4a3ebb7f6/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/6b5edba6682f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/c64b28b0b793/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/263a10faf10b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/6762b78d5496/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34e/7606100/06fd2e9144da/gr4.jpg
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