Potential for lymphatic targeting of peptides

The principle of selective transfer into the lymphatic pathway is primarily based on the structure difference between blood and lymph capillaries. Macromolecules, such as proteins and dextrans, and microparticles, such as colloids, liposomes and mixed micelles, can be used as lymphotropic drug carriers. However, peptide drugs are markedly degraded in the mucosae, various tissues and fluid circulation. The degradation of these drugs by proteolytic enzymes can be prevented by incorporating them into microparticles or chemical conjugation, and lymphatic targeting was achieved by these approaches. Direct injection of such modified drugs into interstitial spaces may result in their high lymphatic recoveries. With respect to drug absorption from the intestine, there are three pathways to the lymph: (a) transcellular lipid pathway, (b) paracellular pathway, and (c) transcytosis via Peyer's patches. The colorectal region is more advantageous for absorption of peptides than the small intestine because there is less enzymatic activity and their absorption can be much improved by absorption enhancers. On the other hand, the pulmonary route is also a potential site for lymphatic delivery of peptide drugs and drug-macromolecular conjugates. This paper reviews the possibility of lymphatic targeting of macromolecular drugs including peptides.