Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/38685
Title: LIPOSOMAL FORMULATION OF RATIONAL COMBINATION OF BIOACTIVE LIPIDS FOR THE TREATMENT OF LEUKEMIA
Authors: TAN KUAN BOONE
Keywords: safingol, C2-ceramide, liposome, acute myeloid leukemia
Issue Date: 18-Feb-2013
Source: TAN KUAN BOONE (2013-02-18). LIPOSOMAL FORMULATION OF RATIONAL COMBINATION OF BIOACTIVE LIPIDS FOR THE TREATMENT OF LEUKEMIA. ScholarBank@NUS Repository.
Abstract: Safingol and C2-ceramide are promising bioactive lipids with activity against leukemia, and combining them to target various aberrant biological processes of AML may further improve therapeutic activity. However, the hydrophobicity and hemolytic toxicities of these bioactive lipids limit their potential to be translated to clinical use. This study hypothesized that an appropriately designed liposome can efficiently incorporate safingol and C2-ceramide to facilitate the delivery of this rational combination of bioactive lipids so as to achieve improved anti-leukemic activity. A synergistic drug ratio of safingol and C2-ceramide was identified and subsequently locked in a liposome carrier. Using this drug delivery strategy, liposomal safingol/C2-ceramide combination had significantly enhanced the survival of the U937-inoculated mice despite 1.5-fold reduction in drug dose, as compared to liposomal safingol or liposomal C2-ceramide alone. The results also highlighted that liposome incorporation was able to significantly attenuate the hemolytic toxicities of the free form of safingol and C2-ceramide.
URI: http://scholarbank.nus.edu.sg/handle/10635/38685
Appears in Collections:Ph.D Theses (Open)

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