Physical methods for enhancing drug absorption from the gastrointestinal tract.

Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Recently, a few approaches that are based on physical interactions, such as magnetic, acoustic, and mechanical forces, have been explored in order to control and improve the drug permeability across the GI mucosa. Although in the early stages, some of these methods have shown great potential both in terms of improved bioavailability and spatiotemporal delivery of drugs. Here, we offer a concise, yet critical overview of these rather unconventional technologies with a particular focus on their potential and possible challenges for further clinical translation.