Delivery systems of ceramide in targeted cancer therapy: ceramide alone or in combination with other anti-tumor agents

Ceramide is a bioactive lipid which functions as a tumor suppressor, regulating processes such as cell proliferation, differentiation, senescence and apoptosis. However, several challenges need to be overcome in order to realize the therapeutic potential of such a bioactive lipid combination regimen, including the hydrophobic and hemolytic nature of the lipids.In this review, we briefly describe the biological function of ceramide, then the delivery systems that have been developed to improve the pharmacology of ceramide have been summarized. In addition, combination therapies based on these delivery systems to reveal the interactions between therapeutic drugs and ceramide were also highlighted. Furthermore, future perspective before the extension of ceramide's applications in cancer treatment will also be discussed.Although ceramide has attracted tremendous attention in targeted cancer treatment, its levels are usually suppressed by over-expression of ceramide-metabolizing enzymes or down-regulation of ceramide-generating enzymes. Thus, finding ways to increase ceramide by exogenous treatment in cancer cells is desired. Therefore, translating these bioactive lipids into clinical usage requires a variety of methods, and appropriately designed delivery systems may play the direct and important role in this process.