Lymphatics drug targeting

J. G. Hall, The lymphatic system in drug targeting An overview, in Targeting of Drugs. Anatomical and Physiological Considerations (G. Gregoriadis and G. Poste, eds.), Plenum Press, New York, 1985, p. 15. 

Muranishi, S. Drug targeting towards lymphatics. Adv. Drug Res. 1991, 21, 1-37. 

Hanatani, K. Takada, K. Yoshida, N. Nakasuji, M. Morishita, Y. Yasako, K. Fujita, T. Yamamoto, A. Muranishi, S. Molecular weight-dependent lymphatic transfer of fluorescein isothiocyanate-labeled dextrans after intrapulmonary administration and effects of various absorption enhancers on the lymphatic transfer of drugs in rats. J. Drug Targeting 1995, 3, 263-271. 

Hall JG. The lymphatic system in drug targeting an overview. In Gregoriadis G, Poste G, eds. Targeting of Drugs—Anatomical and Physiological Considerations. New York Plenum Press, 1985 15. 

The passive targeting of polymeric micelles to solid tumors can be achieved by the enhanced permeability and retention effect (EPR effect). Maeda and his coworkers presented this new drug targeting strategy in 1986 (31,32). As illustrated in Fig. 3, the vascular permeability of tumor tissues is enhanced by the actions of secreted factors such as kinin. As a result of this increased vascular permeability, macromolecules selectively increase their transport from blood vessels to tumor tissues. Furthermore, the lymphatic drainage system does not operate effectively in tumor tissues. 

McHale You made a remark about targeting drugs via the urine. How effective is this We have tried in the past to give drugs to lymphatics intralumenally, and we found that blood-borne drugs are a lot more effective. Have you a different experience ... 

Oussoren C, Storm G. Liposomes to target the lymphatics by subcutaneous administration. Adv Drug Delia Rev 2001 50 143-56. 

Chlorambucil is an anticancer chemotherapeutic agent, used in the treatment of lymphomas. The targeting of this drug to the lymphatic system may improve the treatment of lymphatic cancers. Hence, a prodrug of chlorambucil was synthesized, with the parent drug attached to the 2-position of a triglyceride with palmitic acid in the 1 and 3 positions (Figure 6.6). 

In addition to increased overall bioavailability of lipophilic molecules, lymphatic transport of a drug provides further advantages, including avoidance of hepatic first pass metabolism, a potential to target specific disease states known to spread via the lymphatics, and improved plasma profile of the drug. 

By enhancing the formation and turnover of lymph lipoproteins through the enterocyte and provoking, or improving, the targeting of orally administered lipophilic drugs to the intestinal lymphatics. 

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