SOME PARAMETERS INFLUENCING CYTOTOXICITY OF FREE DOXORUBICIN AND DOXORUBICIN-LOADED NANOPARTICLES IN SENSITIVE AND MULTIDRUG-RESISTANT LEUKEMIC MURINE CELLS - INCUBATION-TIME, NUMBER OF NANOPARTICLES PER CELL

The cytotoxic effect of polyisobutylcyanoacrylate (PIBCA) and polyisohexylcyanoacrylate (PIHCA) nanoparticles, loaded with doxorubicin, was investigated on P388 and P388/ADR-cells, sensitive and resistant to doxorubicin respectively. The nanoparticles formulations were able to reverse the resistance of P388/ADR, although the polymers themselves displayed some cytotoxicity. The influence upon cytotoxicity of parameters such as incubation time, or number of nanoparticles per cell was especially investigated. From those experiments, it appeared that not only the dose of doxorubicin, but also the number of nanoparticles carrying the drug in the cell environment was of first importance: in terms of cytotoxicity, it was preferable to divide the whole dose of doxorubicin into a high number of nanoparticles, even if each nanoparticle was then carrying a lower amount of drug. Some preliminary hypotheses concerning the mechanism of action of the nanoparticles formultions are proposed.