Fate of drug loaded-LNCs in cell culture medium -impact on drug delivery strategies

摘要

Drug delivery, mediated by nanoparticles, relies on nanoparticle stability without drug leakage into the surrounding medium. Furthermore, nanoparticles have to be taken up by the cells and the payload has to be discharged into the cytoplasm. In order to test nanoparticle mediated drug delivery we prepared TETD loaded nanoparticles which were stable in phosphate buffered saline. After mouse fibroblasts were confronted with these nanoparticles cells died at the expected TETD concentration. Since nanoparticles could be visualized inside the cells by confocal laser scanning microscopy it was assumed that cytoplasmic drug delivery was successful. However, after measurement of the amount of free TETD in cell culture medium after transfer of the nanoparticles revealed that TETD was completely discharged from the nanoparticles within several hours. In conclusion, the observed cytotoxicity of TETD loaded nanoparticles is most likely due to premature release of the TETD into the cell culture medium acting through the same pathway as TETD applied directly to cells. Therefore it is essential to test for nanoparticle stability when transferred into another medium.