Journal article
Disposition of Ultrasound Sensitive Polymeric Drug Carrier in a Rat Hepatocellular Carcinoma Model
Academic radiology, v 18(11), pp 1341-1348
2011
PMID: 21971256
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A doxorubicin-loaded microbubble has been developed that can be destroyed with focused ultrasound resulting in fragments, or “nanoshards” capable of escaping through the leaky tumor vasculature, promoting accumulation within the interstitium. This study uses a rat liver cancer model to examine the biodistribution and tumoral delivery of this microbubble platform compared with de novo drug-loaded polymer nanoparticles and free doxorubicin.
Microbubbles (1.8 μm) and 217-nm nanoparticles were prepared containing 14-C labeled doxorubicin. Microbubbles, nanoparticles, a combination of the two, or free doxorubicin were administered intravenously in rats bearing hepatomas, concomitant with tumor insonation. Doxorubicin levels in plasma, organs, and tumors were quantified after 4 hours and 7 and 14 days. Tumors were measured on sacrifice and evaluated with autoradiography and histology.
Animals treated with microbubbles had significantly lower plasma doxorubicin concentrations (0.466 ± 0.068%/mL) compared with free doxorubicin (3.033 ± 0.612%/mL,
P = .0019). Drug levels in the myocardium were significantly lower in animals treated with microbubbles compared to free doxorubicin (0.168%/g tissue vs. 0.320%/g,
P = .0088). Tumors treated with microbubbles showed significantly higher drug levels than tumors treated with free doxorubicin (2.491 ± 0.501 %/g vs. 0.373 ± 0.087 %/g,
P = .0472). These tumors showed significantly less growth than tumors treated with free doxorubicin (
P = .0390).
Doxorubicin loaded microbubbles triggered with ultrasound provided enhanced, sustained drug delivery to tumors, reduced plasma and myocardium doxorubicin levels, and arresting tumor growth. The results suggest that
in situ generation of nano particles provides a superior treatment over injection of free drug and also de novo synthesized nanoparticles.
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Details
- Title
- Disposition of Ultrasound Sensitive Polymeric Drug Carrier in a Rat Hepatocellular Carcinoma Model
- Creators
- Michael C Cochran - School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PAJohn R Eisenbrey - School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PAMichael C Soulen - Division of Interventional Radiology, University of Pennsylvania, Philadelphia, PASusan M Schultz - Department of Radiology, University of Pennsylvania, Philadelphia, PARichard O Ouma - School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PASarah B White - Division of Interventional Radiology, University of Pennsylvania, Philadelphia, PAEmma E Furth - Division of Hepatopathology, University of Pennsylvania, Philadelphia, PAMargaret A Wheatley - School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA
- Publication Details
- Academic radiology, v 18(11), pp 1341-1348
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000296042800003
- Scopus ID
- 2-s2.0-80053579762
- Other Identifier
- 991014878051304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Radiology, Nuclear Medicine & Medical Imaging