ABSTRACT

The dorsal flap chamber, then, provides a literal "window on the microcirculation". Plate 1 * shows a low-magnification montage of the tissue and microvascular blood system of a

transplanted tumor in the window preparation. In the approximately 2-week period since the tumor was seeded, it has grown to a size of -3 mm and has established its own blood supply. It is clear that, unlike the normal blood vessels around it, the tumor microvessels are not well organized; morphologically they run a tortuous and convoluted path. In addition to this vessel tortuosity, such tumor vasculature is typified by venous lakes, regurgitant flow, and stasis. 11 At the endothelial cell level the vessel walls are not structurally complete. It has been shown by others that the blood vessels of many solid tumors are often leaky to circulating macromolecules, such as low-molecular-weight dextrans (70,000 and 150,000 g/mol) and even colloidal carbon (sizes up to 50 nm). 12 It is this feature of increased permeability (especially to colloidal-sized particles) that, when coupled to an ability to keep the liposomal drug supply circulating for an extended period of time, has provided the means to deliver drugs and agents "passively" into the tumor tissue.