Engineering strategies to enhance nanoparticle-mediated oral delivery

Oral delivery is the most preferred route of drug administration due to convenience, patient compliance and cost-effectiveness. Despite these advantages it remains difficult to achieve satisfactory bioavailability levels via oral administration due to the harsh environment of the gastrointestinal (GI) tract, particularly for biomacromolecules. One promising method to increase the bioavailability of macromolecular drugs such as proteins and nucleic acids is to encapsulate them in nanoparticles before oral administration. This review describes innovative strategies for increasing the efficacy of nanoparticle-mediated delivery to the GI tract. Approaches to optimize nanoparticle formulation by exploiting mucoadhesion, environmental responsiveness and external delivery control mechanisms are discussed. The application of recent advances in nanoparticle synthesis using supercritical fluids, microfluidics and imprint lithography to oral delivery are also presented, as well as possible strategies for incorporating nanoparticles into micro- and macroscale oral delivery devices.