Anatomical, Physiological, and Pathological Considerations Relevant for Protein Targeting
Carrier-mediated transport in the body depends on the physicochemical properties of the carrier: its charge, molecular weight/size, surface hydrophobi-city, and the presence of ligands for interaction with surface receptors (Crommelin and Storm, 1990). If a drug enters the circulation and the target site is outside the blood circulation, the drug has to pass through the endothelial barrier. Figure 26 gives a schematic picture of the capillary wall structures (under physiological conditions) present at different locations in the body.
Figure 26 shows a diagram of intact endothelium under normal conditions. Under pathological condi-tions, such as those encountered in tumors inflammation sites, endothelium can differ consider-ably in appearance and endothelial permeability may be widely different from that in “healthy” tissue. Particles with sizes up to about 0.1 mm can enter tumor tissue as was demonstrated with long circulat-ing, colloidal carrier systems (long circulating lipo-somes). On the other hand, necrotic tissue can also hamper access to tumor tissue (Jain, 1987). In conclusion, the body is highly compartmentalized; it should not be considered as one big pool without internal barriers for transport.