Peroral targeting of drug micro or nanocarriers to sites beyond the gastrointestinal tract

Abstract Targeted delivery of drug micro or nanocarriers has been attained via parenteral routes, especially the intravenous route. Conventionally, oral targeting refers to site‐specific delivery and triggered drug release at local sites within the gastrointestinal tract (GIT), or targeting to the enteric epithelia through ligand‐receptor or transporter interactions. Beyond that barrier, the concept of peroral targeting has not been clarified. Nevertheless, this is possible as long as drug carriers are able to be absorbed into the systemic circulation intact. Recent findings on in vivo translocation of drug micro or nanocarriers shed light on potential peroral targeting to remote sites beyond the GIT. Sequential processes of penetration across the enteric epithelia, transportation via the lymphatics and ultimate convergence with the systemic circulation are involved in the underlying mechanisms. The microfold cell (M cell) pathway plays a leading role in breaking through the enteric epithelial barrier. Accumulating evidence confirms primary targeting of a series of lipid and polymeric micro or nanocarriers to organs and tissues of the mononuclear phagocyte systems (MPS), such as the liver, spleen, lungs and kidneys. The total amount of lymph‐bound particles could reach 8%, as evidenced by quantification of glucan microparticles that specifically bind M cell. Migration or translocation of micro or nanocarrier‐bearing macrophages attains secondary targeting of the engulfed micro or nanocarriers to distant sites far beyond the MPS. The current findings foresee a probability of targeting to sites beyond the GIT. However, the content of exposure of micro or nanocarriers at target sites and potential therapeutic or diagnostic promises are yet to be unraveled.