Ultrasound improves the uptake and distribution of liposomal Doxorubicin in prostate cancer xenografts

Ultrasound Med Biol. 2013 Jul;39(7):1255-66. doi: 10.1016/j.ultrasmedbio.2013.02.010. Epub 2013 Apr 30.

Abstract

Combining liposomally encapsulated cytotoxic drugs with ultrasound exposure has improved the therapeutic response to cancer in animal models; however, little is known about the underlying mechanisms. This study focused on investigating the effect of ultrasound exposures (1 MHz and 300 kHz) on the delivery and distribution of liposomal doxorubicin in mice with prostate cancer xenografts. The mice were exposed to ultrasound 24 h after liposome administration to study the effect on release of doxorubicin and its penetration through the extracellular matrix. Optical imaging methods were used to examine the effects at both microscopic subcellular and macroscopic tissue levels. Confocal laser scanning microscopy revealed that ultrasound-exposed tumors had increased levels of released doxorubicin compared with unexposed control tumors and that the distribution of liposomes and doxorubicin through the tumor tissue was improved. Whole-animal optical imaging revealed that liposomes were taken up by both abdominal organs and tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Electroporation / methods*
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate / radiation effects*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Sonication / methods*
  • Tissue Distribution / radiation effects
  • Treatment Outcome
  • Ultrasonic Therapy / methods

Substances

  • Antibiotics, Antineoplastic
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin