The Lymphatic System in Drug Targeting: An Overview

Abstract

The term “drug-targeting” implies that methods may exist for localizing a therapeutic agent on the minority of cells that are actually in need of treatment. Because most cells in most organs and tissues are extravascular they are bathed not in blood but in extravascular tissue fluid. Thus, if a drug is placed in the blood stream (either by direct, intravenous injection or by absorption in the gut after oral administration) it can only reach the target cells by passing across the walls of the smallest blood vessels (capillaries) and entering the local tissue fluid. This process is termed extravasation, and, indeed the tissue fluid itself is formed by the extravasation of water, electrolytes and proteins from the blood plasma. In order to understand how drugs may undergo extravasation it is necessary to understand how normal tissue fluid is formed. Tissue fluid is being formed continually in all capillary beds by the excess of filtration over reabsorption and the resulting clear fluid (which is what the word “lymph” means) has to be drained away continually so that the tissue does not become water-logged and swollen or, in medical terminology, oedematous. These processes can be investigated by collecting lymph fluid and investigating its flow and composition in dynamic terms. If such studies are to give meaningful results they must come from animals that are neither anaesthesised nor restrained.