Improving oral drug bioavailability with polycations?

The administration of drugs via the oral route is challenging due to the (bio)chemical aggressivity of the digestive system and to the presence of barriers that hinder cell uptake and access to the bloodstream. Indeed, the gastrointestinal tract is characterized by large variations of pH, the presence of enzymes and surfactants, and by absorption barriers such as mucus and the epithelium. Thus, many compounds such as proteins and nucleic acids do not reach the systemic circulation due to their premature degradation and/or large size. Among the different strategies that have been investigated to address these challenges, polycations have been explored to improve the oral absorption of many types of drugs. Because of their multiple positive charges and repetitive structure, polycations can protect sensitive drugs against rapid degradation and interact with the gastrointestinal mucosa. Moreover, cationic polymers promote drug transfer across intestinal barriers through various mechanisms, including the opening of the tight junctions, and change in uptake pathway. This contribution provides an overview of the most common polycations currently investigated as absorption enhancers for the oral route, and discusses the manner in which they are employed (co-administration, micro- and nanoparticles, conjugation) to improve the oral drug delivery of different classes of therapeutics.