探索肠道表面受体在口服纳米胰岛素递送中的作用。

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2022-10-01 DOI:10.1124/pharmrev.122.000631
Carlynne Choy, Lee Yong Lim, Lai Wah Chan, Zhixiang Cui, Shirui Mao, Tin Wui Wong
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摘要

在糖尿病治疗中,皮下和吸入胰岛素与针头恐惧症、脂肪肥大、脂肪营养不良和咳嗽有关。口服纳米胰岛素已经开发出来,获得了口服给药的生理益处。本文综述了肠道受体在口服纳米胰岛素靶向递送中的应用。肠道受体靶向改善口服胰岛素的生物利用度并维持血糖降低反应。尽管如此,这些研究都是在小动物模型中进行的,没有优化胰岛素剂量、靶向配体类型和含量、纳米颗粒的物理化学和分子生物学特性对体内/临床糖尿病反应的影响,以及肠道受体群体特征与糖尿病进展的关系。纳米胰岛素和抗糖尿病药物对肠道受体的相互作用,包括它们的上调/下调,是不确定的。甜味受体上调SGLT-1,两者作为纳米胰岛素的新肠道靶点的作用尚不明确。口服纳米胰岛素的受体靶向是一种相对绿色的可行方法,需要深入研究受体及其病理生理特征与口服纳米胰岛素的理化特性之间的关系。意义声明:肠道受体靶向口服纳米胰岛素可提高其生物利用度,并具有持续的降血糖反应。探索新的肠道受体,根据糖尿病患者的病理生理状态定制口服纳米胰岛素的设计,是将胰岛素性能提高到与注射产品相当水平的必要条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Exploring Intestinal Surface Receptors in Oral Nanoinsulin Delivery.

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.

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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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