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DRUG DELIVERY

A new opening for orally taken peptide drugs

Nature Biomedical Engineering volume 4, pages 12–13 (2020)Cite this article

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Negatively charged nanoparticles of about 50 nm in size permit the oral delivery of insulin and other peptide drugs by temporally enhancing the permeability of the intestinal wall.

Delivering drugs orally is simple and non-invasive. Although small-molecule drugs are designed to be readily absorbed after their oral intake, protein and peptide drugs typically do not survive the harsh environment in the gastrointestinal tract and are commonly administered by injection. This is because the main physiological roles of the gastrointestinal tract are to digest non-absorbable food constituents (such as proteins) into small absorbable nutrients and to form a barrier against harmful entities such as bacterial toxins and pathogenic viruses. Peptides can be stabilized against degradation by using bespoke (nano)formulations1 and chemical modifications2, and intestinal absorption can be improved by using barrier-modifying agents (also known as absorption enhancers3) or by targeting transport routes across the intestinal wall4. These strategies have generally led to modest increases in oral bioavailability, and their scaling from rodents to larger animals has been difficult. To circumvent these limitations, ingestible microneedle devices have been designed to inject insulin and other macromolecules into the gastric or intestinal mucosa5,6. Writing in this issue of Nature Biomedical Engineering, Kathryn Whitehead and colleagues now show another unconventional approach to enhancing peptide delivery across the intestinal barrier7: the use of negatively charged silica nanoparticles in a narrow size range, which the researchers show promote the systemic delivery of orally administered peptide drugs (in their case, insulin and the glucagon-like peptide-1 receptor agonist exenatide), without appreciable side effects.

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Fig. 1: Mechanisms of tight junction opening for enhancing the permeability of the intestinal wall.

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Authors and Affiliations

  1. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    Per Artursson & Patrik Lundquist

  2. Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Per Artursson

Authors
  1. Per Artursson
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  2. Patrik Lundquist
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Correspondence to Per Artursson.

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The authors declare no competing interests.

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Artursson, P., Lundquist, P. A new opening for orally taken peptide drugs. Nat Biomed Eng 4, 12–13 (2020). https://doi.org/10.1038/s41551-019-0513-1

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