ABSTRACT

Introduction

Intestinal permeation enhancers (PEs) are substances that transiently alter the intestinal epithelial barrier to facilitate permeation of macromolecules with low oral bioavailability (BA). While a number of PEs have progressed to clinical testing in conventional formulations with macromolecules, there has been only low single digit increases in oral BA, irrespective of whether the drug met primary or secondary clinical endpoints.

Areas covered

This article considers the causes of sub-optimal BA of macromolecules from PE dosage forms and suggests approaches that may improve performance in humans.

Expert opinion

Permeation enhancement is most effective when the PE is co-localized with the macromolecule at the epithelial surface. Conditions in the GI tract impede optimal co-localization. Novel delivery systems that limit dilution and spreading of the PE and macromolecule in the small intestine have attempted to replicate promising enhancement efficacy observed in static drug delivery models.

中文翻译：

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肠道渗透促进剂可改善大分子的口服生物利用度：对人体低效的原因

抽象的

介绍

肠渗透促进剂（PEs）是会短暂改变肠上皮屏障以促进大分子低口服生物利用度（BA）渗透的物质。尽管许多PE均已开始使用具有大分子的常规制剂进行临床测试，但是无论药物是否达到主要或次要临床终点，口服BA的增幅均较低。

覆盖区域

本文考虑了来自PE剂型的大分子BA欠佳的原因，并提出了可能改善人类性能的方法。

专家意见

当PE与大分子在上皮表面共定位时，渗透增强是最有效的。胃肠道中的条件阻碍了最佳共定位。限制PE和大分子在小肠中稀释和扩散的新型递送系统已尝试复制在静态药物递送模型中观察到的有希望的增强功效。