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Enhancement of radiotherapeutic effectiveness by temperature-sensitive liposomal 1-methylxanthine

Authors
Jeong, Seong-YunYi, So LyoungLim, Sun-KyungPark, Sung-JinJung, JooheeWoo, Ha NaSong, Si YeolKim, Jin-SeokLee, Jung ShinLee, Jin SeongPark, Heon JooChoi, Eun Kyung
Issue Date
8-May-2009
Publisher
ELSEVIER SCIENCE BV
Keywords
1-Methylxanthine; Radiosensitivity; Temperature-sensitive; Liposome; Xenograft
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.372, no.1-2, pp 132 - 139
Pages
8
Journal Title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume
372
Number
1-2
Start Page
132
End Page
139
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13757
DOI
10.1016/j.ijpharm.2008.12.040
ISSN
0378-5173
1873-3476
Abstract
Most of methylxanthine derivatives including caffeine have been known to radiosensitize cancer cells, but the obstacles such as toxicity, request of high dose and poor solubility hinder their preclinical evaluations and clinical applications. In this study, we evaluated the efficacy of 1-methylxanthine (1-MTX), a caffeine metabolite as a radiosensitizer and the in vivo effectiveness of the temperature-sensitive liposomal 1-methylxanthine (tsl-MTX) in combination with ionizing radiation and regional hyperthermia. In human colorectal and lung cancer cells, treatment of 1-MTX sensitized cells to ionizing radiation. To evaluate the in vivo capability of 1-MTX to radiosensitize tumors, we developed temperature-sensitive liposomal 1-MTX using DPPC:DMPC:DSPC (4:1:1 molar ratio) with intention of overcoming lethal toxicity of 1-MTX and controlling drug-release. The particle size of the liposomes was approximately 200 mm in diameter. The release of 1-MTX from the liposomes was responding to increase of temperature. In xenograft tumor-bearing mice, the tsl-MTX administered using the i.p. route showed delay of tumor growth. Importantly, tsl-MTX in combination with radiation and regional hyperthermia exhibited marked delay of tumor growth, suggesting that 1-MTX effectively enhanced radiation-induced suppression of tumor growth. In conclusion, tsl-MTX has highly efficacious anticancer competence in vivo, enhancing radiotherapeutic effectiveness, and feasibility for further clinical applications. (c) 2009 Elsevier B.V. All rights reserved.
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