Oral peptide delivery: prioritizing the leading technologies

In the late 1980s and early 1990s, oral delivery technologies for macromolecules, peptides and proteins mushroomed at tremendous rates due to a number of very promising preclinical studies. Interest from pharmaceutical companies in these technologies subsequently fell away from in the late 1990s owing to a series of clinical disappointments as many supposed ‘platform technologies’ failed for a variety of reasons: very low oral bioavailability, toxicity and lack of study reproducibility. Other factors that were implicated in the demise of these programs included formulation and scale-up issues, which prevented the required translation to man. Many lessons were learnt in this period and we are now in a very interesting phase where several delivery technologies are in advanced clinical trials for oral peptides [1,2] and one has now successfully completed the Phase III trials [201]. From our extensive reading of the literature however, one can really get no sense of which oral delivery technologies have been discontinued. For the ones that are still in play, their current status is difficult to ascertain. Moreover, the shift in the field towards translational success for a few technologies with relatively low-molecular weight payloads is not apparent in recent literature.

PMID 22833982  /  David J Brayden, Randall J Mrsny