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  • Review Article
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Materials for oral delivery of proteins and peptides

Nature Reviews Materials volume 5, pages 127–148 (2020)Cite this article

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Abstract

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.

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Fig. 1: Key technological advances towards the oral delivery of proteins and peptides.
Fig. 2: Physiological barriers to oral protein and peptide delivery.
Fig. 3: Mechanisms of action of materials used for oral drug delivery.
Fig. 4: Materials used for oral protein and peptide delivery as a function of length scale.

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Change history

  • 08 January 2020

    The originally published article contained a typographical error in the final text box of Figure 1, which has been corrected in the HTML and PDF versions of the manuscript.

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Acknowledgements

S.M. acknowledges funding from Blavatnik Biomedical Accelerator of Harvard University. T.D.B. acknowledges funding from the National Science Foundation (NSF) Graduate Research Fellowship (DGE-1745303). K.A.W. was supported by NSF grant number 1807983.

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Authors and Affiliations

  1. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Tyler D. Brown & Samir Mitragotri

  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

    Tyler D. Brown & Samir Mitragotri

  3. Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA

    Kathryn A. Whitehead

  4. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA

    Kathryn A. Whitehead

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S.M., T.D.B. and K.A.W. contributed to discussions of the article content, writing and review or editing of the manuscript before submission. T.D.B. additionally researched data for the article.

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Correspondence to Samir Mitragotri.

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Competing interests

S.M. declares that he is a shareholder and director of i2O Therapeutics, which is developing oral-drug-delivery products based on ionic liquids, and acts as a consultant and as a member of the advisory board of Entrega Bio. T.D.B. declares that he is a shareholder and employee of i2O Therapeutics. K.A.W. declares no competing interests.

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Brown, T.D., Whitehead, K.A. & Mitragotri, S. Materials for oral delivery of proteins and peptides. Nat Rev Mater 5, 127–148 (2020). https://doi.org/10.1038/s41578-019-0156-6

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