Walsh Edwin G, Adamczyk Bozena E, Chalasani Kishore B, Maher Sam, O'Toole Edel B, Fox John S, Leonard Thomas W, Brayden David J
UCD School of Veterinary Medicine & Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Ther Deliv. 2011 Dec;2(12):1595-610. doi: 10.4155/tde.11.132.
Oral delivery of macromolecular drugs, particularly peptides and proteins, is the focus of many academic and industrial laboratories. Armed with an increased understanding of the structure and regulation of intestinal epithelial junctional complexes of the paracellular barrier, the development of permeation enhancement technology initially focused on the specific and reversible opening of tight junctions in order to enable oral delivery. Despite intense research, none of these specific tight junction-opening technologies has yet been approved in an oral drug product, likely because of poor efficacy. Less specific enhancer technologies with a long history of safe use in man have additional surfactant-like effects on the transcellular pathway that lead to improved efficacy. These are likely to be the first to market for selected poorly permeable peptides. This review presents a summary of some approaches taken to intestinal permeation enhancement and explores in detail the oral delivery system developed by Merrion Pharmaceuticals, Gastrointestinal Permeation Enhancement Technology (GIPET).
大分子药物的口服给药，尤其是肽类和蛋白质类药物，是许多学术和工业实验室的研究重点。随着对细胞旁屏障肠道上皮连接复合体的结构和调节有了更多了解，渗透增强技术的发展最初集中在紧密连接的特异性和可逆性开放上，以便实现口服给药。尽管进行了深入研究，但这些特异性紧密连接开放技术中没有一种在口服药物产品中获得批准，可能是因为疗效不佳。在人类中有长期安全使用历史的非特异性增强技术对跨细胞途径有额外的表面活性剂样作用，从而提高了疗效。这些技术可能会率先用于某些渗透性差的肽类药物上市。本文综述了一些肠道渗透增强方法，并详细探讨了Merrion制药公司开发的口服给药系统——胃肠道渗透增强技术（GIPET）。
