肠道淋巴生物学、给药和治疗:现状与未来方向。

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2024-10-16 DOI:10.1124/pharmrev.123.001159
Sanjeevini Babu Reddiar, Yining Xie, Mohammad Abdallah, Sifei Han, Luojuan Hu, Orlagh M Feeney, Gracia Gracia, Abel Anshabo, Zijun Lu, Muhammad Asim Farooq, Ian K Styles, Anthony R J Phillips, John A Windsor, Christopher J H Porter, Enyuan Cao, Natalie L Trevaskis
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引用次数: 0

摘要

一直以来,人们认为肠道淋巴管是体液、免疫细胞、膳食脂质、脂溶性维生素和亲脂药物的被动通道。20 世纪末对肠淋巴给药的研究主要集中在药物的理化特性上,尤其是导致肠淋巴运输的高亲脂性。最近的发现改变了我们的传统观点,证明淋巴管在一系列生物和病理过程中,包括在肠道内,是活跃的、可塑的和组织特异性的角色。这些发现反过来又激发了人们对一系列疾病的淋巴特异性疗法的探索,并开发出更复杂的策略,包括一系列纳米技术、脂质原药和在淋巴运输途径上 "搭便车 "的脂质共轭材料,主动向肠淋巴输送药物或疫苗。随着新型生物疗法的不断发展,人们开始关注这些新型疗法在口服后是否能通过肠道淋巴吸收和转运。在此,我们回顾了目前对健康和疾病中胃肠道淋巴系统解剖学和生理学的理解,重点是与给药相关的方面。我们总结了当前最先进的给药方法,并量化了药物在肠道淋巴系统中的吸收情况。最后,令人兴奋的是,我们讨论了最近通过肠道淋巴给药取得显著药代动力学和治疗效果的实例。我们还提出了在未来推进肠道淋巴给药策略的开发和临床应用的方法。意义声明 这篇综合性综述详细介绍了健康和疾病中肠淋巴系统的解剖和生理学知识,重点关注与给药相关的方面。它重点介绍了当前向肠淋巴管给药的最先进方法,以及使用这些策略为患者带来药代动力学和治疗益处的转变。
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Intestinal Lymphatic Biology, Drug Delivery, and Therapeutics: Current Status and Future Directions.

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins, and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20th century focused primarily on the drugs' physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic, and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs, and lipid-conjugated materials that "hitchhike" onto lymphatic transport pathways. With the increasing development of novel therapeutics such as biologics, there has been interest in whether these therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarize the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies in the future. SIGNIFICANCE STATEMENT: This comprehensive review details the understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients.

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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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