Overcoming the intestinal barrier: A look into targeting approaches for improved oral drug delivery systems

Oral drug administration is one of the most preferred and simplest routes among both patients and formulation scientists. Nevertheless, orally delivery of some of the most widely used therapeutic agents (e.g., anticancer drugs, peptides, proteins and vaccines) is still a major challenge due to the limited oral bioavailability associated with them. The poor oral bioavailability of such drugs is attributed to one or many factors, such as poor aqueous solubility, poor permeability, and enzymatic degradation. Various technological strategies (such as permeation enhancers, prodrugs and nanocarriers) have been developed to enhance the bioavailability of these drugs after oral administration. Among the different approaches, advanced and innovative drug delivery systems, especially targeting-based strategies, have garnered tremendous attention. Furthermore, the presence of numerous types of cells and solute carrier transporters throughout the gastrointestinal tract represents numerous potential targeting sites for successful oral delivery that have not yet been exploited for their full potential. This review describes different targeting strategies towards different targeting sites in the gastrointestinal tract. Additionally, exciting improvements in oral drug delivery systems with different targeting strategies (e.g., M cells for oral vaccination and L cells for type 2 diabetes mellitus) are also discussed.