Progress and limitations of oral peptide delivery as a potentially transformative therapy

Numerous formulation technologies have been developed to overcome challenges of oral peptide delivery. Understanding the advantages and limitations of each technology is important for the development of new delivery systems to enable oral delivery of peptides designed for parenteral administration.

This review summarizes key learnings from the use of permeation enhancers (PEs) for oral peptide delivery associated with solid dosage form optimization to maximize the PE effect. Furthermore, we will highlight the most recent emerging delivery strategies to improve oral peptide bioavailability such as nanoparticles, self-emulsifying drug delivery systems, gut shuttles, and ingestible devices. In addition, advantages and limitations of these technologies will be compared with the permeation enhancer technology.

Despite the success of permeation enhancer technology in the FDA-approved oral peptide products, oral peptide delivery is still facing the immense challenge of low-to-single digit oral bioavailability. Optimization of drug product attributes such as dissolution kinetics is critical to improve permeation enhancer efficacy. The next frontiers to substantially increase oral bioavailability and transform injectable peptides to oral deliverables may be ingestible devices and ligand-mediated transport (gut shuttles). However, clinical studies are necessary to inform the safety and efficacy of these emerging technologies.