Administration of drugs using small (<100 nm) unilamellar liposomes enables effective targeting of tumors and inflamed tissue. Therapeutic efficacy may be enhanced by triggering liposomal drug release in the desired organ in a controlled manner using a noninvasive external signal. Previous studies have demonstrated that low frequency ultrasound (LFUS) can be used to control the release of drugs from liposomes. LFUS irradiation has a twofold effect: (1) it causes the impermeable liposome membrane to become permeable and (2) it induces liposome disintegration. Immediately upon cessation of LFUS irradiation the membrane resumes its impermeable state and liposome disintegration stops. The mathematical model presented here is aimed at providing a better quantitative and qualitative understanding of LFUS-induced liposomal drug release, which is essential for safe and effective implementation of this technique. The time-dependent release patterns are determined by the liposome disintegration patterns and by two key parameters: (a) the average permeability of the membrane to the drug and (b) the ratio between the volume of the entire dispersion and the initial volume of all the liposomes in the dispersion. The present model implies that LFUS irradiation triggers two liposomal drug-release mechanisms: the predominant one is diffusion through the LFUS-compromised liposome membrane, and the less significant one is liposome disintegration.
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The authors thank Prof. Eitan Kimmel for valuable discussions and Ms. Ilana Nisky for her assistance in the statistical analysis. AS is grateful to the Israel Ministry of Science and Technology for the Eshkol Scholarship, as well as to the Barenholz Fund and to The Research Council of Norway for their support.
Author information Authors and AffiliationsDepartment of Biomedical Engineering, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva, 84105, Israel
Giora Enden
Department of Chemical Engineering, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva, 84105, Israel
Avi Schroeder
The Laboratory of Liposome and Membrane Research, Department of Biochemistry, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem, 91120, Israel
Avi Schroeder
Correspondence to Giora Enden.
Additional informationThe work was performed at the Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
About this article Cite this articleEnden, G., Schroeder, A. A Mathematical Model of Drug Release from Liposomes by Low Frequency Ultrasound. Ann Biomed Eng 37, 2640–2645 (2009). https://doi.org/10.1007/s10439-009-9785-z
Received: 25 May 2009
Accepted: 19 August 2009
Published: 03 September 2009
Issue Date: December 2009
DOI: https://doi.org/10.1007/s10439-009-9785-z
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