Liposomal codelivery of a synergistic combination of bioactive lipids in the treatment of acute myeloid leukemia.

Aim: The aim of this work was to develop a liposomal formulation to facilitate delivery of a synergistic safingol/C2-ceramide combination in the treatment of acute myeloid leukemia (AML).

Materials & Methods: Liposomes were prepared using the extrusion method and the bioactive lipids were encapsulated passively. Drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Role of reactive oxygen species in the synergistic cytotoxicity of safingol-based combination regimens with conventional chemotherapeutics.

Exploiting the sensitivity of cancer cells to reactive oxygen species (ROS) has been suggested as a strategy for the selective elimination of cancer cells. In this study, the ROS-generating sphingolipid safingol was combined with various conventional chemotherapeutics, and the potential synergism of the safingol-based combination regimen was assessed using a panel of cancer cell lines. The IC(50) values of safingol using as a single agent were 1.

In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia.

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.

Lipid-based nanoparticulate systems for the delivery of anti-cancer drug cocktails: Implications on pharmacokinetics and drug toxicities.

The use of drug cocktails has become a widely adopted strategy in clinical cancer therapy. Cytotoxic drug cocktails are often administered based on maximum tolerated dose (MTD) of each agent, with the belief of achieving maximum cell kill through tolerable toxicity level. Yet, MTD administration may not have fully captured the therapeutic synergism that exists among the individual agents in the drug cocktail, as the response to a cocktail regimen, that is, whether the effect is synergistic or not, could be highly sensitive to the concentration ratios of the individual drugs at the site of action.

The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells.

Colon cancer represents one of the most common solid tumors in adults. Although 5-fluorouracil (5-FU) and irinotecan have been frequently administered in colon cancer patients, low response rates to these single drug therapies were reported. It is therefore imperative to search for new targeted combination therapies that are effective.