Objective:Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs.
Methods:hTe following nanocarriers were studied:micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods:dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto-and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice atfer the pulmonary or intravenous delivery.
Results:Signiifcant differences in lung uptake were found atfer the inhalation delivery of lipid-based and non-lipid-based nanoparticles. hTe accumulation of liposomes and micelles in lungs remained relatively high even 24 h atfer inhalation when compared with MSNs, QDs, and PPI dendrimers. hTere were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h atfer inhalation or intravenous administrations, but 24 h atfer intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes signiifcantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer.
Conclusion:hTe results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers atfer the inhalation delivery. hTese particles are most suitable for effective inhalation treatment of lung cancer.