Induction of pro-inflammatory cytokines by traditional and nano formulations of anti-cancer drug Paclitaxel

Abstract Paclitaxel is a natural product with known anti-cancer activity. Paclitaxel is insoluble in water and requires the use of delivery vehicle. Historically two formulations of this drug were introduced into clinic: traditional, known as Taxol®, and more recently, nanotechnology-based, named Abraxane®. Several studies have reported that in murine macrophages Paclitaxel mimics endotoxin in induction of expression of several proinflammatory genes, and have suggested that Paclitaxel and endotoxin share the same receptor (TLR4) to initiate inflammatory signalling. These earlier studies utilized traditional formulation Taxol®. Nanotechnology offers many benefits to drug delivery such as reduction of drug toxicity, change in its biodistribution and controlled drug release. Clinical use of Abraxane® demonstrated decreased toxicity of this formulation as compared to that of Taxol®, however no study comparing cytokine induction profile of Paclitaxel in nano and traditional formulations has been reported so far. We have revisited this question and conducted an in vitro study evaluating induction of proinflammatory cytokines by traditional and nano formulations of Paclitaxel. Taxol®, but not Abraxane® resulted in induction of proinflammatory cytokines. This data was consistent between three cell culture models - whole blood, PBMC and MonoMac6 cell line. The mechanisms of cytokine induction by Taxol® will be discussed.