Abstract
Chemotherapy is one of the frontline treatments for cancer patients, but the toxic side effects limit its effectiveness and potential. The goal of drug delivery is to reduce these side effects by encapsulating the drugs in a carrier which prevents release and can circulate throughout the body causing minimal damage to the healthy tissue. Slow release carriers have been developed which reduce the exposure to healthy tissue but this slow release also limits the maximum levels of drug in the tumor and nonspecific accumulation in healthy tissue remains a major hurdle. The next advance is to design these carriers to produce a rapid burst release of drug, but only in response to a localized trigger. The trigger of choice is low intensity focused ultrasound. A new particle is described here which incorporates an ultrasound sensitive microbubble of perfluorocarbon gas within a protective liposome carrier along with the payload. It is shown that this design can accomplish the desired burst release when exposed to ultrasound focused to small spatial locations within tissue phantoms. The ability to trigger release could provide a second level of spatial and temporal control beyond biochemical targeting or passive accumulation, making these promising particles for further development.
Stuart Ibsen and Michael Benchimol contributed equally to this work.
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Acknowledgements
The authors are grateful for the insightful discussions with Ahmet Erten while conducting these experiments. The study was supported by the NCI Grant No. 5U54CA119335-05, and by the UCSD Cancer Center Specialized Support Grant P30 CA23100.
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Ibsen, S., Benchimol, M., Simberg, D., Esener, S. (2012). Ultrasound Mediated Localized Drug Delivery. In: Zahavy, E., Ordentlich, A., Yitzhaki, S., Shafferman, A. (eds) Nano-Biotechnology for Biomedical and Diagnostic Research. Advances in Experimental Medicine and Biology, vol 733. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2555-3_14
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