Throughout history, oral administration has been regarded as the most convenient mode of drug delivery, as it requires minimal expertise and invasiveness. Although oral delivery works well for small-molecule drugs, oral delivery of macromolecules (particularly proteins and peptides) has been limited by acidic conditions in the stomach and low permeability across the intestinal epithelium. Accordingly, the large numbers of biologic drugs that have become available in the past 10 years typically require administration by injection or infusion. As such, a renewed emphasis has been placed on the development of novel materials that overcome the physiological challenges of oral delivery for macromolecular agents. This Review provides an overview of physiological barriers to the oral delivery of biologics and highlights the advances made in materials across various length scales, from small molecules to macroscopic devices. This Review also describes the current status of materials for oral delivery of protein and peptide drugs.

纵观整个历史，口服给药被认为是最方便的药物递送方式，因为它需要最少的专业知识和侵入性。尽管口服递送对于小分子药物效果很好，但是大分子（尤其是蛋白质和多肽）的口服递送受到胃中酸性条件和肠上皮低渗透性的限制。因此，在过去的10年中可获得的大量生物药物通常需要通过注射或输注来施用。因此，人们将新的重点放在了新材料的开发上，这些材料克服了大分子药物口服给药的生理挑战。这篇综述概述了口服生物制剂的生理障碍，并重点介绍了从小分子到宏观装置等各种长度尺度的材料所取得的进步。该评价还描述了口服蛋白质和肽类药物的材料的现状。