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|Title:||In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia|
|Keywords:||Acute myeloid leukemia|
|Citation:||Tan, K.-B., Ling, L.-U., Bunte, R.M., Chng, W.-J., Chiu, G.N.C. (2012-06-10). In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia. Journal of Controlled Release 160 (2) : 290-298. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jconrel.2011.11.002|
|Abstract:||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. © 2011 Elsevier B.V.|
|Source Title:||Journal of Controlled Release|
|Appears in Collections:||Staff Publications|
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