A comprehensive review of the strategies to improve oral drug absorption with special emphasis on the cellular and molecular mechanisms

Oral drug delivery is the most convenient and cost-effective route of administration, due to which most of the drugs are administered through the oral route. Apparently, oral delivery is the easiest approach for drug administration; however, in reality, it is one of the most complicated routes. Although the gastrointestinal (GI) tract offers a large surface area for absorption, the GI epithelium is designed for the permeation of molecules with a specific set of physicochemical properties only. Due to this, different drugs exhibit considerable variabilities in absorption; one can show more than 90% absorption, while others may show less than 10%. To improve the oral absorption of low bioavailable drugs, multiple strategies have been developed, with variable success. To design a successful strategy, a thorough understanding of the GI physiology and the mechanism of drug absorption is pivotal. Different parts of the GI tract have significant variations, all of which have a profound impact on drug absorption. In this comprehensive review, we have done a cross-disciplinary exploration of the cellular physiology of different barriers present in the GI tract, how they impact drug absorption, and also discussed the diverse strategies developed to overcome absorption barriers present in the GI tract.