کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2504659 1557473 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhancement of radiotherapeutic effectiveness by temperature-sensitive liposomal 1-methylxanthine
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Enhancement of radiotherapeutic effectiveness by temperature-sensitive liposomal 1-methylxanthine
چکیده انگلیسی

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 nm 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 372, Issues 1–2, 8 May 2009, Pages 132–139
نویسندگان
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