Moreover, a single dose of 1mg ZOL is able to induce a significant reduction of circulating
VEGF in patients with bone metastases suggesting an in vivo biological activity of low ZOL concentrations in humans . 6. Nanotechnology and BPs: Macrophage Targeting overnight delivery Macrophages are the major differentiating cell of the mononuclear phagocyte system (MPS). They derive from monocytes that migrate from Inhibitors,research,lifescience,medical the peripheral blood to extravascular tissue where they differentiate into macrophages . Macrophages play a critical role in host defense because they migrated to an infected focus following attraction by a variety of substances, such as components from bacteria, complement components, immune complexes, and collagen fragments. Once at the infected focus, macrophages may phagocytose and kill infectious agents by a variety of mechanisms . Moreover, following uptake of protein antigens, macrophages generated immunogenic fragments activating Inhibitors,research,lifescience,medical and regulating the immune sellckchem response . Finally, macrophages infiltrate
tumors, Inhibitors,research,lifescience,medical where they represent an important mechanism of host defense against tumor cells, either inhibiting tumor cell division or killing the cells following secretion of soluble mediators or by other means [97, 98]. However, most tumors can be infiltrated by a different macrophage phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, these tumor-associated macrophages (TAM) secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression . Thus, due to their pivotal role in a number of physiological and pathological processes including tumors, Inhibitors,research,lifescience,medical macrophages represent an attractive target for therapy. While in the case
of small soluble drug, only a small fraction can reach the macrophages, these latter can be the preferential accumulation site for intravenously injected colloidal carriers. Indeed, once into the bloodstream plasma proteins adsorb on particle surface and this process, also named opsonization, facilitates particle recognition and Inhibitors,research,lifescience,medical clearance from the blood by circulating phagocytes as well as tissue macrophages that are in direct contact with the blood . Thus, the localization Drug_discovery of intravenously injected nanocarriers in cells of the mononuclear phagocytes system (MPS) offers a potential and powerful method to target therapeutic agents to these cells. Nowadays, various lipid and polymeric carriers such as liposomes and nanoparticle are under investigation to deliver drugs to macrophages. However, nanocarrier characteristics, in terms of size, shape, and particle surface, affect the pharmacokinetics of the nanocarrier and need to be carefully evaluated when designing nanocarriers for macrophage targeting. For more details, the readers are directed to more specific reviews on this theme, for example, an excellent review by Moghimi .