Teniposide-loaded multilayer modified albumin nanoparticles with increased passive delivery to the lung

Abstract

The nature of a particle surface has a tremendous influence on the in vitro and in vivo behavior of the particle, in addition to the particle size. In this study, multilayer modified albumin nanoparticles were developed to encapsulate teniposide, an anti-cancer agent used in the treatment of lung cancer, in order to optimize its distribution and pharmacokinetics. Multilayer nanoparticles were prepared by coating albumin particles with chitosan and subsequently with PLG–PEG. The multilayer structure was confirmed by the increase in particle size, reverse potential, surface components and morphology, suggesting a layer by layer coating mechanism, involving electrostatic interaction. According to the results of the in vitro release and cytotoxicity studies, the multilayer particles were slightly pH-sensitive to an acidic environment. More importantly, compared with the commercial injection, the modified particles showed a preference for distribution in the lung and exhibited far lower concentrations in the heart and kidney and a prolonged circulation in plasma after intravenous injection, whereas the naked albumin nanoparticles mainly accumulated in the liver and spleen. In addition, P-CS-NP with a reduced amount of PLG–PEG transiently and extensively accumulated in the lung but then rapidly migrated to the liver or spleen, suggesting that the amount of coated layer on the particles affected the targeting behavior and retention in the lung. Therefore, the structure of the albumin core and multi-coated layers are a very promising way for achieving controlled release and passively targeted delivery to the lung.