Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles.

Abstract

The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation steps, and the interaction between sound waves and microbubbles generates biological effects that can be beneficial for the successful delivery of nanocarriers and their contents. In this study, a novel platform consisting of nanoparticle-stabilized microbubbles has been investigated for its potential for ultrasound-enhanced delivery to tumor xenografts. Confocal laser scanning microscopy was used to study the supply of nanoparticles from the vasculature and to evaluate the effect of different ultrasound parameters at a microscopic level. The results demonstrated that although the delivery is heterogeneous within tumors, there is a significant improvement in the delivery and the microscopic distribution of both nanoparticles and a released model drug when the nanoparticles are combined with microbubbles and ultrasound. The mechanisms that underlie the improved delivery are discussed.

• Authors: Siv Eggen, Stein-Martin Fagerland, Ýrr Mørch, Rune Hansen, Kishia Søvik, Sigrid Berg, Håkon Furu, Audun Dybvik Bøhn, Magnus B Lilledahl, Anders Angelsen, Bjørn Angelsen, Catharina de Lange Davies
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 187 Pg. 39-49 (Aug 10 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 24852099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Polyethylene Glycols
• Enbucrilate

Topics

• Animals
• Cell Line, Tumor
• Drug Delivery Systems
• Enbucrilate (chemistry)
• Heterografts (metabolism)
• Humans
• Male
• Mice, Nude
• Microbubbles
• Nanoparticles (administration & dosage, chemistry)
• Polyethylene Glycols (chemistry)
• Prostatic Neoplasms (metabolism)
• Ultrasonics