Enhanced antitumor efficacy of gemcitabine-loaded temperature-sensitive liposome by hyperthermia in tumor-bearing mice.

INTRODUCTION

Gemcitabine-loaded TSL (Gem-TSL) was used in combination with hyperthermia (HT) to treat the colon adenocarcinoma-bearing BALB/c mice for improved anticancer effect following intravenous administration.

METHODS

A new temperature-sensitive liposome (TSL), composed of DPPC:DMPC:DSPC (4:1:1 molar ratio) releasing the encapsulated gemcitabine (Gem) at 41 °C, was developed and evaluated for enhanced antitumor efficacy both in vitro and in vivo.

RESULTS

Drug release from the TSL was sharply increased at 41 °C and in vitro cytotoxicity of Gem-TSL in colon adenocarcinoma cells (CT-26) was 10 times higher than the free drug (IC50 = 0.3 μM versus 3 μM). Apoptosis seemed to be the main mechanism of cell death as the treatment of the cells with Gem-TSL increased the caspse-3/7 activity by 1.5-fold and also caused the fragmentation of chromatin DNA. Gem-TSL suppressed the tumor growth in CT-26-bearing BALB/c mice more stronger than the free gemcitabine after intravenous administration. Moreover, this in vivo antitumor efficacy of Gem-TSL was further increased when HT was added.

DISCUSSION

This study suggests that this new TSL-Gem formulation could serve as a new chemotherapy modality together with HT.