- 著者
- Kosuke Shimizu Miki Takada Tomohiro Asai Kenji Irimura Kazuhiko Baba Naoto Oku
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.25, no.6, pp.783-786, 2002 (Released:2002-06-01)
- 参考文献数
- 19
- 被引用文献数
- 10 13
To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4β-aminoalkyl-4′-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.
- 著者
- Kosuke Shimizu Miki Takada Tomohiro Asai Koichi Kuromi Kazuhiko Baba Naoto Oku
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.25, no.10, pp.1385-1387, 2002 (Released:2002-10-01)
- 参考文献数
- 19
- 被引用文献数
- 6 8
A novel anti-tumor agent, 6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103), effectively inhibits both topoisomerase I and II activities. To enhance anti-tumor efficacy and to reduce the side effects of the agent, liposomalization of TAS-103 was performed. TAS-103 was effectively entrapped in liposomes by a remote-loading method, and was stable at 4 °C and in the presence of 50% serum. To evaluate the anti-tumor efficacy of liposomal TAS-103, the growth inhibition against Lewis lung carcinoma cells in vitro and the therapeutic efficacy against solid tumor-bearing mice in vivo were examined. Liposomal TAS-103 showed strong cytotoxic effect against Lewis lung carcinoma cells in a dose dependent manner and effectively suppressed solid tumor growth accompanying longer survival time of tumor-bearing mice in comparison with the mice treated with free TAS-103. These results suggest that liposomal TAS-103 is useful for cancer therapy.