title: Enhancement of Small Molecule Delivery by Pulsed High-Intensity Focused Ultrasound: A Parameter Exploration.
abstract: 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.
authors.affiliation: School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA. Electronic address: ynwang@u.washington.edu.
authors.forename: Yak-Nam
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington, USA.
authors.forename: Navid
authors.initials: N
authors.lastname: Farr
authors.affiliation: Division of Gastroenterology, School of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Zia
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Asan, Korea.
authors.forename: Bong Min
authors.initials: BM
authors.lastname: Ko
authors.affiliation: Division of Gastroenterology, School of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Khokhlova
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA; Division of Gastroenterology, School of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Joo Ha
authors.initials: JH
authors.lastname: Hwang
mesh_terms: D000818:Animals; D004058:Diffusion / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005070:Evans Blue / Q000737:chemistry* / Q000528:radiation effects*; D019220:High-Energy Shock Waves; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D066298:In Vitro Techniques; D007668:Kidney / Q000737:chemistry* / Q000528:radiation effects*; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D013552:Swine
chemical_list: D005070:Evans Blue
keywords: Content and penetration; Drug delivery; Kidney; Pulsed-high intensity focused ultrasound; Ultrasound parameters