Enhancing Tumor Drug Distribution With Ultrasound-Triggered Nanobubbles

被引:61
作者
Nittayacharn, Pinunta [1 ]
Yuan, Hai-Xia [2 ,3 ]
Hernandez, Christopher [1 ]
Bielecki, Peter [1 ]
Zhou, Haoyan [4 ]
Exner, Agata A. [1 ,3 ]
机构
[1] Case Western Reserve Univ, Dept Biomed Engn, 10900 Euclid Ave, Cleveland, OH 44106 USA
[2] Fudan Univ, Dept Ultrasound, Zhongshan Hosp, 180 Fenglin Rd, Shanghai 200032, Peoples R China
[3] Case Western Reserve Univ, Dept Radiol, 10900 Euclid Ave, Cleveland, OH 44106 USA
[4] GSK 1250 S Collegeville Rd, Collegeville, PA 19426 USA
基金
美国国家卫生研究院;
关键词
cavitation; sonoporation; ultrasound; nanobubbles; doxorubicin; drug delivery; CHANGE CONTRAST AGENTS; BLOOD-BRAIN-BARRIER; RETENTION EPR; DOXORUBICIN DELIVERY; MICELLES; RELEASE; MICROBUBBLES; NANOPARTICLES; PERMEABILITY; LIPOSOMES;
D O I
10.1016/j.xphs.2019.05.004
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Issues with limited intratumoral drug penetration and heterogeneous drug distribution continue to impede the therapeutic efficacy of nanomedicine-based delivery systems. Ultrasound (US)-enhanced drug delivery has emerged as one effective means of overcoming these challenges. Acoustic cavitation in the presence of nanoparticles has shown to increase the cellular uptake and distribution of chemotherapeutic agents in vivo. In this study, we investigated the potential of a drug-loaded echogenic nanoscale bubbles in combination with low frequency (3 MHz), high energy (2 W/cm(2)) US for antitumor therapy. The doxorubicin-loaded nanobubbles (Dox-NBs) stabilized with an interpenetrating polymer mesh were 171.5 +/- 20.9 nm in diameter. When used in combination with therapeutic US, Dox-NBs combined with free drug showed significantly higher (*p < 0.05) intracellular uptake and therapeutic efficacy compared with free drug. When injected intravenously in vivo, Dox-NBs thorn therapeutic US showed significantly higher (*p < 0.05) accumulation and better distribution of Dox in tumors when compared with free drug. This strategy provides an effective and simple method to increase the local dose and distribution of otherwise systemically toxic chemotherapeutic agents for cancer therapies. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:3091 / 3098
页数:8
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