Abstract
The use of liposomes as carriers for chemotherapeutic agents in combination with ultrasound as a stimulus to control the time and space of the drug release is a promising approach for cancer treatment, as it can reduce the side effects caused by conventional chemotherapy. This in vitro study investigated the triggered release of calcein from stealth (PEGylated) and non-stealth (non-PEGylated) liposomes, using ultrasound at low (20 kHz) and high (1 and 3 MHz) frequencies, and at different power densities. Release was monitored by the increase in fluorescence due to relieving of calcein’s self-quenching upon dilution when the model drug leaks out of the liposomes. The results showed that, independent of the power density, the release was highest at 20 kHz. For the same frequency, release usually increased with increasing power densities. Additionally, for release at 20 kHz, a comparison was done for PEGylated and non-PEGylated liposomes, at two pH values: 5.2 and 7.4. The results were then compared to previously published studies. In all cases, the mechanism of release seems to involve cavitation events that either pierce a hole in or shear open the liposomes, as all the determined power densities are above the transient cavitation threshold.
About the authors
Salma E. Ahmed obtained her BSc degree in Chemical Engineering from the University of Khartoum, Sudan, in 2011, where she worked as a laboratory assistant upon graduation. Afterwards she joined the Master’s program in Chemical Engineering at the American University of Sharjah (AUS) UAE, where she was awarded a graduate assistantship to continue her studies. Mrs. Ahmed’s research area of interest is drug delivery systems. She has been working on developing novel liposomal drug delivery systems for cancer treatment since she joined AUS in 2012, first as a Master’s student, then as a research assistant. Currently she is working as a research associate of Biomedical Engineering in Khalifa University of Science, Technology and Research (KUSTAR), Abu Dhabi, UAE.
Hesham G. Moussa obtained his BSc (2013) and MSc (2015) degrees in Electrical Engineering from the American University of Sharjah (AUS), where he worked as a teaching assistant and a research assistant for 3 years. As a recipient of a graduate assistantship award, he worked as a lab assistant for multiple courses during his MSc studies. His research interest is in biomedical engineering. During his undergraduate years, Hesham worked in the field of assistive biomedical devices and, in 2012, he began a collaboration with the Chemical Engineering Department at AUS, on developing novel liposomal drug delivery systems for cancer treatment. After graduating, he continued working as a research assistant in the Ultrasound in Cancer Research Group. In January 2016, Hesham will start his PhD in the Electrical Engineering, in the University of Waterloo, Canada. He authored one review and three conference papers.
Ana M. Martins is a research scientist at the Ultrasound in Cancer Research Group at American University of Sharjah. She obtained her BSc in Biochemistry and her PhD in Biochemistry/Enzymology from the University of Lisbon, Portugal. Dr. Martins has a wide research experience: after completing her PhD she spent 7 years at Virginia Polytechnic Institute and State University (USA), first at the Virginia Bioinformatics Institute, later at the Department of Biological Sciences. Dr. Martins has a systems biology approach to research, combining experimental and modeling studies to understand the function of biochemical systems. Her current research interests include the development of drug delivery systems using liposomes and ultrasound as a trigger. She was the recipient of several awards, including PhD and postdoctoral fellowships from the Portuguese Science Foundation.
Mohammad H. Al-Sayah is an Associate Professor of Chemistry at the Department of Biology, Chemistry and Environmental Sciences at the American University of Sharjah (AUS), UAE. He holds a PhD in Physical Organic Chemistry from University of Alberta, Canada and a MSc and a BSc in Chemistry from the American University of Beirut, Lebanon. His research expertise spans a broad range of chemistry including supramolecular chemistry, organic chemistry, chemical biology, nanotechnology and material science with 50+ publications and conference presentations. Dr. Al-Sayah is a recipient of several prestigious awards and grants including the Distinguished Scholar Award from the Arab Fund Fellowship Program (Kuwait), the VSP Grant from the Office of Naval Research Global (UK), the COMSTECH Award (Greece), and a Sabbatical Leave Award (AUS) to Harvard University.
Ghaleb A. Husseini (BSc 1995–MSc 1997–PhD 2001) graduated with a PhD in Chemical Engineering (Biomedical Engineering emphasis) from Brigham Young University in 2001 and joined the American University of Sharjah as an Assistant Professor in the Chemical Engineering Department in 2004. He was promoted to an Associate Professor and Professor in 2008 and 2013, respectively. Four years ago, Dr. Husseini took a sabbatical leave which enabled him to travel to the Ecole Polytechnique Fédérale de Lausanne (EPFL, and work in Dr. Jeffrey Hubbell’s laboratory). Dr. Husseini works in the area of ultrasound-activated drug delivery. His research involves sequestering chemotherapeutic agents in liposomes, micelles and other nanoparticles, and studying their controlled release triggered by ultrasound. Dr. Husseini has recently established the Ultrasound in Cancer Research Group at AUS using an internal grant. He has published 76 journal articles (in addition to one book chapter and one patent) and 40 conference papers/abstracts. He has been elected into the Distinguished Lecturer Program-IEEE-Engineering in Medicine and Biology Society (January 2014–December 2015).
Acknowledgments
The authors would like to acknowledge the funding from the American University of Sharjah Faculty Research Grant (FRG1-2012), Patient’s Friends Committee-Sharjah, and Al Qasimi Foundation. The authors would also like to acknowledge Dr. Nasser Qaddoumi from the Department of Electrical Engineering, American University of Sharjah for his help with the high frequency release experiments.
Conflict of interest statement: Authors state no conflict of interest. All authors have read the journal’s Publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.
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