Enhanced antitumor efficacy of gemcitabine-loaded temperature-sensitive liposome by hyperthermia in tumor-bearing mice
- Authors
- Lim, Sun-Kyung; Shin, Dae Hwan; Choi, Mi-Hee; Kim, Jin-Seok
- Issue Date
- Apr-2014
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- Colon cancer therapy; gemcitabine; hyperthermia; temperature-sensitive liposomes
- Citation
- DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, v.40, no.4, pp 470 - 476
- Pages
- 7
- Journal Title
- DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
- Volume
- 40
- Number
- 4
- Start Page
- 470
- End Page
- 476
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10938
- DOI
- 10.3109/03639045.2013.768631
- ISSN
- 0363-9045
1520-5762
- Abstract
- 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 degrees 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 degrees 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 mu M versus 3 mu M). 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.
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