Lymphatic transport system to circumvent hepatic metabolism for oral delivery of lipid-based nanocarriers

The oral route of administration for lipid-based nanocarriers is of immense importance for the drugs having low bioavailability because of extensive first-pass metabolism. These drug delivery systems have reportedly improved oral bioavailability via lymphatic transport. The solubility issues of a drug are addressed by directly encapsulating them into the lipid. Subsequently, various lipid-based nanocarriers have enhanced the therapeutic activity of drugs via lymphatic transport with negligible side effects. Animal studies have depicted significant improvement in the oral bioavailability of drugs by avoiding first-pass metabolism. A detailed clinical study for large animals is needed to investigate the safety and efficacy of various lipid-based nanocarriers. In this review, we have described the potential and pertinence of the oral route of administration for lipid-based nanocarriers. The importance of lymphatic transport systems as a liver bypass transport system is also described herein. Various carriers such as liposomes, nanostructured lipid carriers, lipid-drug conjugate, etc. are discussed in brief with recent examples. The transport of lipids and absorption of drugs across the lymphatic pathway and various factors associated with nanocarriers affecting the lymph node targeting are also highlighted. Various in vivo and in vitro research models along with a brief focus on in silico prediction of the lymphatic transfer are described. The insights on future perspectives with an emphasis on the translational barriers may help the researchers working in this area.