کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1424627 986731 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia
چکیده انگلیسی

Prognosis of patients with acute myeloid leukemia (AML) remains poor despite the use of first-line induction chemotherapy. Therefore, it is imperative to find effective treatment for AML patients. Safingol is a bioactive sphingolipid which has demonstrated promising in vitro anti-leukemic properties; however, translation into clinical use is hampered by its low water solubility and dose-limiting hemolysis. The present study is the first to describe a rationally designed liposome formulation of safingol and demonstrate the anti-leukemic potential using a panel of human AML cell lines and patient samples as well as a human xenograft model in SCID mice. Encapsulation efficiency of safingol into liposomes was approximately 100%, and the release of drug followed square-root-of-time release model. The presence of a transmembrane pH gradient completely abolished the biological activity of liposomal safingol. A positive zeta potential, which influenced cellular accumulation of liposomal safingol, was crucial to the anti-leukemic activity. Liposomal safingol was effective against a wide range of AML subtypes with minimal hemolytic toxicity, and was able to extend the median survival time of the U937-inoculated mice to 31 days as compared to 23 days by free drug. The increase in therapeutic efficacy could be related to the increase in systemic drug exposure as a result of liposome encapsulation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 160, Issue 2, 10 June 2012, Pages 290–298
نویسندگان
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