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Disposition of ultrasound sensitive polymeric drug carrier in a rat hepatocellular carcinoma model. Acad Radiol 2011 Nov;18(11):1341-8

Date

10/06/2011

Pubmed ID

21971256

Pubmed Central ID

PMC3188389

DOI

10.1016/j.acra.2011.06.013

Scopus ID

2-s2.0-80053579762   49 Citations

Abstract

RATIONALE AND OBJECTIVES: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Author List

Cochran MC, Eisenbrey JR, Soulen MC, Schultz SM, Ouma RO, White SB, Furth EE, Wheatley MA

Author

Sarah B. White MD, MS, FSIR, FCIRSE Vice Chair, Professor in the Radiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Antibiotics, Antineoplastic
Autoradiography
Carbon Radioisotopes
Carcinoma, Hepatocellular
Disease Models, Animal
Doxorubicin
Drug Carriers
Liver Neoplasms, Experimental
Microbubbles
Nanoparticles
Polymers
Rats
Tumor Cells, Cultured