Increase of doxorubicin penetration in cultured rat hepatocytes by its binding to polymethacrylic nanoparticles

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Abstract

The anticancer agent, doxorubicin (DXR), was bound to a particulate carrier consisting of polymethacrylic nanospheres (0.3 μm diameter). The uptake of free and nanoparticle-bound doxorubicin in adult rat hepatocytes maintained in primary culture was compared using high-performance liquid chromatography. At concentrations ranging from 50 to 500 ng DXR/ml of nutrient medium, neither free nor bound DXR induced cytotoxicity, as evidenced by light microscopy and leakage of lactate dehydrogenase. In the case of doxorubicin-loaded nanoparticles compared to free DXR, after a 24 h incubation, DXR concentrations in the hepatocytes were increased by 64% and 25% for respectively initial concentrations of 50 and 500 ng DXR/ml of medium. Moreover, the endocytosis of the nanospheres by the hepatocytes was observed by electron microscopic examination. These results emphasize the usefulness of polymethacrylic nanoparticles as a new intracellular carrier for the enhancement of the penetration of drugs, such as anthracyclines, into cells.

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