Lymphatic Absorption of Orally Administered Prodrugs

This paper presents an overview of the anatomy, physiology, and biology of the lymphatic system specifically relevant to lymphatic drug delivery. We will briefly review the classic fluid and solute transport literature, and also examine the current research in lymphatic endothelial cell biology and tumor metastasis in the lymphatics because of the increasing potential for targeted delivery of immunomodulators, chemotherapeutics, and genetic material to specific lymph nodes (Refs. [1-7]).

The current state of the art of intestinal lymphatic transport is given by reviewing the more recent publications, which have utilized lipid-based vehicles. The results published often show variable trends depending on, the design of the vehicle, the components used, the physicochemical properties of the drug, the animal model and experimental techniques, these variables often make direct comparisons difficult. Traditionally intestinal lymphatic delivery has been expressed as a percentage of the dose transported in the lymph. Using this parameter results obtained to date, with lipid-based vehicles, are somewhat disappointing maximising at approximately 20-30%, for highly lipophilic compounds including DDT and halofantrine (Hf). Recent data, monitoring Hf, in a fed versus fasted dog study, have shown that a higher degree of lymphatic transport is possible (>50% dose) in the postprandial state, this study should result in stimulating renewed interest in the potential of achieving significant levels of lymphatic targeting. Although some relevant features controlling lymphatic transport have been identified over the years a deeper appreciation of all the mechanisms, which is vital for therapeutic exploitation of lymphatic transport, is still unrealized. This review analyses the success and limitations of a formulation approach using lipid-based vehicles and highlights potential areas for further research.