Ultrasound enhanced antitumor activity of liposomal doxorubicin in mice

Abstract

Liposomal encapsulation of doxorubicin (DXR) improves tumor accumulation and reduces adverse effects. One possible strategy for further optimization of this delivery technology would be to design the liposome carrier to release its content within the tumor tissue in response to specific stimuli such as ultrasound (US). In this study, the tumor uptake properties and therapeutic efficacy of 1,2 distearoyl-sn-glycero-3-phosphatidylethanolamine-based liposomes containing DXR were investigated in nude mice bearing tumor xenografts. The liposomal DXR formulation alone showed no inhibitory effect on tumor growth. However, upon exposure to low frequency US in situ inhibition of tumor growth was demonstrated.

Keywords::

• Therapeutic effect
• low frequency ultrasound
• drug delivery
• drug release

Acknowledgements

We thank Professor Knut A. Hagtvet, University of Oslo, for valuable advice regarding statistical analysis, as well as Sibylla Røgnvaldsson and Ulrich M. W. Eide for technical assistance. We also like to thank Professor F. Saatcioglu, University of Oslo, for providing the CWR22 xenograft model.

Declaration of interest

The project is supported by the NANOMAT programme, the Norwegian Research Council. TJE, SLF, EAN have ownership interests in Epitarget AS. EH and DRO have no such interests in Epitarget AS and report no conflict of interest. The authors alone are responsible for the content and writing of the manuscript, and the decision to publish.