Journal article
Delivery of Encapsulated Doxorubicin by Ultrasound-Mediated Size Reduction of Drug-Loaded Polymer Contrast Agents
IEEE transactions on biomedical engineering, v 57(1), pp 24-28
Jan 2010
PMID: 19709952
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Low delivery efficiency combined with systemic toxicity of traditional chemotherapy provides a need for improved chemotherapeutic delivery. Within our laboratory, we have developed polymer ultrasound contrast agents (1.2-1.8 ¿m in diameter) containing doxorubicin (Dox) within the shell (100-150 nm). In vivo this platform is expected to circulate through the vasculature until activated at the tumor site with external focused ultrasound (US). In vitro , the agent is responsive to US and when insonated at peak positive pressure amplitudes of 0.69 MPa and above, shows dramatic size reduction, eventually reaching a mean particle size of 350 nm, presumably due to fragmentation of, or gas release from the agent. The resulting Dox-polymer particles retain the drug and are small enough to pass through the leaky pores (350-400 nm) within the tumor vasculature, providing a sustained intratumoral release of chemotherapeutic as the polymer degrades. In vivo studies using a VX2 liver tumor model have shown that the combination of the agent and US results in nearly 50% less drug delivered to the nontargeted, healthy liver ( p = 0.009) and a 110% increase ( p = 0.004) in Dox delivery to the viable peripheral tissue of the tumor, relative to the uninsonated controls. This study shows how US-mediated destruction of drug-loaded polymer contrast agent can be used to deliver encapsulated drug for potential sustained release. Penetration mechanisms of these resulting particles and their ability to provide a sustained release from the tumor interstia will be explored in the future.
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Details
- Title
- Delivery of Encapsulated Doxorubicin by Ultrasound-Mediated Size Reduction of Drug-Loaded Polymer Contrast Agents
- Creators
- J. R Eisenbrey - School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia , USAM. C Soulen - Department of Radiology Hospital , University of Pennsylvania, Philadelphia, USAM. A Wheatley $^$ - School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, USA
- Publication Details
- IEEE transactions on biomedical engineering, v 57(1), pp 24-28
- Publisher
- IEEE
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000273565600006
- Scopus ID
- 2-s2.0-76649116508
- Other Identifier
- 991014877829804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical