Overcoming poor permeability: translating permeation enhancers for oral peptide delivery

Demand for oral alternatives to parenteral delivery has led to renewed interest in excipient-like intestinal permeation enhancers that improve oral drug bioavailability. Oral delivery of macromolecules including peptides and proteins is limited by pre-systemic degradation and poor penetration across the gut wall. Research on oral absorption enhancers that increase gut permeability was first undertaken 50 years ago, yet clinical success has yet to be achieved. Development has been hampered by lack of adequate reproducible efficacy as well as perceived safety concerns. We review some selected permeation-enhancing excipients that are key components of peptide formulations in advanced clinical development and assess why translation of such technologies is close to fruition.

Graphical abstractOral delivery of hydrophilic macromolecules is impeded by poor permeation across the intestinal epithelium. Use of absorption enhancers in enteric-coated formulations improve permeability.Figure optionsDownload full-size imageDownload high-quality image (146 K)Download as PowerPoint slide