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Drug Dev Ind Pharm. 2014 Apr;40(4):470-6. doi: 10.3109/03639045.2013.768631. Epub 2013 Apr 24.

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

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  • 1Research Center for Cell Fate Control (RCCFC), College of Pharmacy, Sookmyung Women's University , Seoul , South Korea.



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.


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.


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.


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

[PubMed - indexed for MEDLINE]
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