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J Control Release. 2014 Aug 10;187:39-49. doi: 10.1016/j.jconrel.2014.05.020. Epub 2014 May 20.

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

Author information

1
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: siv.eggen@ntnu.no.
2
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
3
SINTEF Materials and Chemistry, Dept. of Polymer Particles and Surface Chemistry, Trondheim, Norway.
4
SINTEF Technology and Society, Dept. of Medical Technology, Trondheim, Norway; Department of Circulation and Diagnostic Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
5
SINTEF Technology and Society, Dept. of Medical Technology, Trondheim, Norway.
6
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Urological Surgery, St. Olavs Hospital, Trondheim University Hospital, Norway.
7
Department of Circulation and Diagnostic Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

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.

KEYWORDS:

Drug delivery; Microbubbles; Microdistribution; Nanoparticles; Solid tumor; Ultrasound

PMID:
24852099
DOI:
10.1016/j.jconrel.2014.05.020
[Indexed for MEDLINE]

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