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Drug Delivery through Phagocytosis of Red Blood Cells

2004; Karger Publishers; Volume: 31; Issue: 2 Linguagem: Inglês

10.1159/000078042

1660-3818

Sonja Serafini, Luigia Rossi, A. Antonelli, Alessandra Fraternale, Aurora Cerasi, Rita Crinelli, Laura Chiarantini, Giuditta Fiorella Schiavano, Mauro Magnani,

Pancreatic function and diabetes

Human red blood cells, once in circulation, survive for 120 days and are then removed through an immunomediated mechanism by resident macrophages. We have taken advantage of these unique properties to develop a new drug delivery system. In fact, a number of conventional and new drugs can be encapsulated into human erythrocytes by several procedures. Once re-infused in the same donor the circulating red cells behave as a slow drug delivery system. Alternatively, drug-loaded red cells can be modified to increase their phagocytosis by inducing band 3 clustering and opsonization by autologous IgGs and complement (up to C3b). Macrophages recognize and phagocytose such drug-loaded red cells through the Fc and C3b receptors. This drug targeting system permits the administration of membrane-impermeable molecules to macrophages and allows to optimize treatment of human infections by a number of pathogens with a tropism for macrophages. Furthermore, as reviewed in this paper, modified red cells can be conveniently used to deliver peptides, modified proteins, antisense nucleotides, or small organic molecules. The red cell-based drug targeting system has been proved to be effective and safe in preclinical studies. The administration of drugs by autologous red cells has been proved to be effective in humans with more than 600 administrations.