Controlling liposomal drug release with low frequency ultrasound: Mechanism and feasibility

Avi Schroeder, Yuval Avnir, Sarah Weisman, Yousef Najajreh, Alberto Gabizon, Yeshayahu Talmon, Joseph Kost, Yechezkel Barenholz

Research output: Contribution to journalArticlepeer-review

209 Scopus citations


The ability of low-frequency ultrasound (LFUS) to release encapsulated drugs from sterically stabilized liposomes in a controlled manner was demonstrated. Three liposomal formulations having identical lipid bilayer compositions and a similar size (∼100 nm) but differing in their encapsulated drugs and methods of drug loading have been tested. Two of the drugs, doxorubicin and methylpredinisolone hemisuccinate, were remote loaded by transmembrane gradients (ammonium sulfate and calcium acetate, respectively). The third drug, cisplatin, was loaded passively into the liposomes. For all three formulations, a short exposure to LFUS (<3 min) released nearly 80% of the drug. The magnitude of drug release was a function of LFUS amplitude and actual exposure time, irrespective of whether irradiation was pulsed or continuous. Furthermore, no change in liposome size distribution or in the chemical properties of the lipids or of the released drugs occurred due to exposure to LFUS. Based on our results, we propose that the mechanism of release is a transient introduction of porelike defects in the liposome membrane, which occurs only during exposure to LFUS, after which the membrane reseals. This explains the observed uptake of the membrane-impermeable fluorophore pyranine from the extraliposomal medium during exposure to LFUS. The implications of these findings for clinical applications of controlled drug release from liposomes are discussed.

Original languageEnglish
Pages (from-to)4019-4025
Number of pages7
Issue number7
StatePublished - 27 Mar 2007

ASJC Scopus subject areas

  • General Materials Science
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry


Dive into the research topics of 'Controlling liposomal drug release with low frequency ultrasound: Mechanism and feasibility'. Together they form a unique fingerprint.

Cite this