Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Oct 15, 2018
WEB OF SCIENCETM
checked on Oct 15, 2018
checked on May 19, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.