Materials for oral delivery of proteins and peptides

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. New materials, beyond those that have already obtained regulatory approval, are needed to improve the bioavailability of orally administered proteins. In this Review, barriers to the oral delivery of protein-based therapies are discussed, along with the current translational landscape and state of the art of materials for oral protein delivery.