Approaches to oral drug delivery for challenging molecules.

Advances in biotechnology, high throughput screening and computational chemistry have led to a considerable increase in the number of protein and peptide therapeutics and other macromolecular drugs. Working with macromolecules, however, poses a number of challenges that must be overcome to successfully develop these compounds into safe and effective therapeutics. Significant efforts in pharmaceutical and academic laboratories have been expended in finding ways to deliver macromolecular drug molecules by the oral route, which can significantly improve patient compliance, convenience, and efficacy. Nevertheless, for a drug molecule to be orally bioavailable, it has to overcome the natural physiological processes of breaking down molecules in the gastrointestinal tract, and to traverse a relatively impermeable epithelial layer of cells that line the gastrointestinal tract. This article provides a summary of the challenges that researchers need to surmount in the development of orally absorbable peptide and protein drugs, and gives an overview of the novel approaches currently in progress in the field of oral delivery.