Dendrimer-TPGS mixed micelles for enhanced solubility and cellular toxicity of taxanes

Taxanes are the most effective, efficient and broad spectrum anticancer drugs for the treatment of various cancers. However, poor aqueous solubility is the major problem in their delivery at higher concentrations in cancer cells. In this research work, poor solubility of taxanes is addressed by preparing dendrimer and D-a-tocopherol polyethylene glycol succinate (TPGS) mixed micelles by taking into consideration the advantages of TPGS such as solubility enhancement and P-glycoprotein inhibition. Dendrimer TPGS mixed micelles were prepared by solvent casting method. Docetaxel (DTX) and paclitaxel (PTX) were chosen as model drugs representing the group of taxanes. Nanomicelles were characterized by DLS, FTIR, PXRD, in vitro drug release and hemolytic studies. Effects of pH and dendrimer to TPGS ratio on the solubility of taxanes were also studied. Solubility of DTX and PTX were increased by 20.36 and 34.95 folds, respectively, when formulated in dendrimer TPGS mixed micelles. Drug release studies exhibited better release profile of encapsulated drug at acidic pH which is advantageous in enhanced intracellular drug release in cancer cells. Formulations were found to be biocompatible in hemolytic toxicity assay. Cytotoxicity studies revealed that anticancer activities of both drugs were enhanced after encapsulation in micelles against cancer cells while caused very low toxicity to normal cells. Thus, dendrimer TPGS mixed micelles are promising alternate for delivery of poorly water-soluble drugs taxanes. (C) 2014 Elsevier B.V. All rights reserved.