POTENTIAL FOR LYMPHATIC TARGETING OF PEPTIDES

The principle of selective transfer into the lymphatic pathway is prim arily based on the structure difference between blood and lymph capill aries. Macromolecules, such as proteins and dextrans, and microparticl es, such as colloids, liposomes and mixed micelles, can be used as lym photropic 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 incorporati ng them into microparticles or chemical conjugation, and lymphatic tar geting was achieved by these approaches. Direct injection of such modi fied 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 c olorectal 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 deli very of peptide drugs and drug-macromolecular conjugates. This paper r eviews the possibility of lymphatic targeting of macromolecular drugs including peptides.