TY - JOUR
T1 - Enhancement of Small Molecule Delivery by Pulsed High-Intensity Focused Ultrasound
T2 - A Parameter Exploration
AU - Zhou, Yufeng
AU - Wang, Yak Nam
AU - Farr, Navid
AU - Zia, Jasmine
AU - Chen, Hong
AU - Ko, Bong Min
AU - Khokhlova, Tatiana
AU - Li, Tong
AU - Hwang, Joo Ha
N1 - Funding Information:
This work was supported by National Institutes of Health Grants 1 R01 CA154451 and 5 R03 DK084126-02 and the Washington State Life Science Discovery Fund .
Publisher Copyright:
© 2016 World Federation for Ultrasound in Medicine & Biology.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Chemotherapeutic drug delivery is often ineffective within solid tumors, but increasing the drug dose would result in systemic toxicity. The use of high-intensity focused ultrasound (HIFU) has the potential to enhance penetration of small molecules. However, operation parameters need to be optimized before the use of chemotherapeutic drugs in vivo and translation to clinical trials. In this study, the effects of pulsed HIFU (pHIFU) parameters (spatial-average pulse-average intensity, duty factor and pulse repetition frequency) on the penetration as well as content of small molecules were evaluated in ex vivo porcine kidneys. Specific HIFU parameters resulted in more than 40 times greater Evans blue content and 3.5 times the penetration depth compared with untreated samples. When selected parameters were applied to porcine kidneys in vivo, a 2.3-fold increase in concentration was obtained after a 2-min exposure to pHIFU. Pulsed HIFU has been found to be an effective modality to enhance both the concentration and penetration depth of small molecules in tissue using the optimized HIFU parameters. Although, performed in normal tissue, this study has the promise of translation into tumor tissue.
AB - Chemotherapeutic drug delivery is often ineffective within solid tumors, but increasing the drug dose would result in systemic toxicity. The use of high-intensity focused ultrasound (HIFU) has the potential to enhance penetration of small molecules. However, operation parameters need to be optimized before the use of chemotherapeutic drugs in vivo and translation to clinical trials. In this study, the effects of pulsed HIFU (pHIFU) parameters (spatial-average pulse-average intensity, duty factor and pulse repetition frequency) on the penetration as well as content of small molecules were evaluated in ex vivo porcine kidneys. Specific HIFU parameters resulted in more than 40 times greater Evans blue content and 3.5 times the penetration depth compared with untreated samples. When selected parameters were applied to porcine kidneys in vivo, a 2.3-fold increase in concentration was obtained after a 2-min exposure to pHIFU. Pulsed HIFU has been found to be an effective modality to enhance both the concentration and penetration depth of small molecules in tissue using the optimized HIFU parameters. Although, performed in normal tissue, this study has the promise of translation into tumor tissue.
KW - Content and penetration
KW - Drug delivery
KW - Kidney
KW - Pulsed-high intensity focused ultrasound
KW - Ultrasound parameters
UR - http://www.scopus.com/inward/record.url?scp=84961285668&partnerID=8YFLogxK
U2 - 10.1016/j.ultrasmedbio.2015.12.009
DO - 10.1016/j.ultrasmedbio.2015.12.009
M3 - Article
C2 - 26803389
AN - SCOPUS:84961285668
SN - 0301-5629
VL - 42
SP - 956
EP - 963
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 4
ER -