Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond

Pharm Res. 2013 Oct;30(10):2675-93. doi: 10.1007/s11095-013-1093-5. Epub 2013 Jun 12.


Purpose: The presence of 7-epidocetaxel in docetaxel injection and in vivo epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization in vivo. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.

Methods: The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The in vivo toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.

Results: B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better in vivo stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced in vitro cytotoxicity, against A549 and B16F10 cells, than Taxotere®.

Conclusion: We can therefore expect less in vivo conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further in vivo studies are needed to ascertain these facts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Docetaxel
  • Drug Carriers / chemistry*
  • Female
  • Humans
  • Liposomes
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Polyethylene Glycols / chemistry*
  • Solubility
  • Stereoisomerism
  • Surface Properties
  • Taxoids / administration & dosage*
  • Taxoids / adverse effects
  • Taxoids / chemistry
  • Taxoids / therapeutic use


  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Taxoids
  • Docetaxel
  • Polyethylene Glycols