Drug resistance reversal activity of anticancer drug loaded solid lipid nanoparticles in multi-drug resistant cancer cells

Abstract

The aim of our study was to enhance the cytotoxicity of anticancer drugs by reversing the resistance of multi-drug resistant cancer cells. The cytotoxicities of paclitaxel (PTX) and doxorubicin (DOX), either as single agents or loaded in solid lipid nanoparticles (SLN) by a solvent diffusion method, were examined using drug sensitive cancer cells and drug resistant cells by measuring the drug concentration required for 50% growth inhibition (IC50). Compared to Taxol and DOX·HCl solution, both PTX and DOX loaded in SLN exhibited higher cytotoxicities in human breast tumor drug sensitive MCF-7 and drug resistant MCF-7/ADR cells. The ability of PTX loaded SLN and DOX loaded SLN to reverse the drug resistance of MCF-7 cells compared to MCF-7/ADR cells was 31.0 and 4.3 fold, respectively. Both PTX and DOX loaded SLN showed the same trends of enhanced cytotoxicity against a second wild type/drug resistant human ovarian cancer cell pair SKOV3 and SKOV3-TR30 cells. The reversal powers were 3.8 and 1.9 fold for PTX loaded SLN and DOX loaded SLN, respectively.