2018 Volume 33 Issue 5 Pages 377-389
Oral administration is preferred route for pharmacotherapy, but there are many drugs that are not effective orally due to insufficient stability and low permeability of gastrointestinal membrane. Transcellular permeation are mediated by specific transporters and endocytosis as well as nonspecific lipophilicity-dependent simple diffusion. In this article, transporters that may affect permeability of drugs and could be used as the target of intestinal delivery of drugs are described, including both absorptive influx and excretory efflux transporters. Many reports demonstrated that several drugs are absorbed as the substrates of influx transporters. In addition, there are challenge of a chemical modification of active drug molecule as prodrug to be substrate of influx transporters. Known influx drug transporters are peptide transporter PEPT1, nucleoside transporters CNTs and ENTs, organic anion/cation transporters OATP2B1 and OCTs, and bile acid transporter ASBT/IBAT. When efflux transporters suppress intestinal drug absorption, certain excipients used for formulation of drugs have a potential to inhibit P-glycoprotein. Usually substrates of transporters are small molecules with molecular weight less than about 1,000. Endocytosis could be applied for the absorption enhancement of biological large molecule drugs. Since transporters are membrane proteins and could be surface receptor to recognize their substrates as ligands, utilization of nanoparticles labeled with transporter substrates (ligands) could be targeted to the transporters, resulting in delivery of the cargo in the particles. Accordingly, transporters are promising targets to design DDS to improve absorption of both of small and large molecular drugs by variable approaches. In this review, we focus on current approaches and future possibilities of oral DDS targeting intestinal transporters.
