Drug delivery

Nanoparticles bound to red blood cells (RBCs) could be used to deliver drugs to the vasculature of specific organs. The method involves mixing bare nanogels with ex vivo RBCs to enable RBC-nanoparticle binding, then injecting the RBC-bound nanoparticles either IV for lung targeting, or into an artery immediately upstream of other target organs. In ex vivo human lungs, RBC-bound nanoparticles accumulated in higher levels compared with unbound nanoparticles. In mice, RBC-bound nanoparticles had higher lung-specific accumulation and lung-to-liver ratio of accumulation than unbound nanoparticles. Also in mice, intra-arterial injection of RBC-bound nanoparticles to the right internal carotid artery, renal artery or common carotid artery increased accumulation and organ-to-blood ratio in the brain, left kidney and right side of face, respectively. In pigs, IV injection of RBC cell-bound nanoparticles also increased lung-to-blood ratio of nanoparticles. In a mouse model of pulmonary embolism, RBC-bound nanoparticles loaded with Retavase reteplase increased pulmonary emboli dissolution and decreased pulmonary embolism burden as measured by number of fibrin or fibrinogen clots remaining in lungs compared with unbound, Retavase-loaded nanoparticles. Next steps could include testing the organ-specific delivery of RBC-bound nanoparticles in other animal models of acute cardiovascular or pulmonary disease...