Site-Specific Impact of a Regional Hydrodynamic Injection: Computed Tomography Study during Hydrodynamic Injection Targeting the Swine Liver

Pharmaceutics

Takeshi Yokoo¹  Tsutomu Kanefuji²  Takeshi Suda²  Kenya Kamimura¹  Dexi Liu³  Shuji Terai¹ 

[1] Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata 950-8510, Japan; E-Mails:;Department of Gastroenterology & Hepatology, Uonuma Institute of Community Medicine, Niigata University, 4132 Urasa, Minami Uonuma, Niigata, 949-7392, Japan; E-Mail:;Department of Pharmaceutical and Biochemical Sciences, University of Georgia, College of Pharmacy, 250 W. Green street, Athens, GA 30602, USA; E-Mail:

关键词: hydrodynamic gene delivery;    swine;    computed tomography;    interventional radiology;    regional application;    hemodynamics;   

DOI  :  10.3390/pharmaceutics7030334

来源: mdpi

【 摘 要 】

A hemodynamic study of hydrodynamic gene delivery (HGD) from the tail vein in rodents has inspired a mechanism and an approach to further improve the efficacy of this procedure. However, there is no report on the hemodynamics of a regional HGD, which is an inevitable approach in large animals. Here, we report the hemodynamics of a regional hydrodynamic injection in detail based on 3D volume data and the dynamism of tissue intensity over time by using computed tomography (CT) both during and after a regional hydrodynamic injection that targeted the liver of a pig weighing 15.6 kg. Contrast medium (CM) was injected at a steady speed of 20 mL/s for 7.5 s under the temporal balloon occlusion of the hepatic vein (HV). A retrograde flow formed a wedge-shaped strong enhancement area downstream of the corresponding HV within 2.5 s, which was followed by drainage into another HV beginning from the target area and the portal vein (PV) toward a non-target area of the liver. After the injection, the CM was readily eliminated from the PV outside the target area. These data suggest that an interventional radiology approach is effective in limiting the hydrodynamic impacts in large animals at a target area and that the burden overflowing into the PV is limited. A further investigation that simultaneously evaluates gene delivery efficiency and hemodynamics using CT is needed to establish feasible parameters for a regional HGD in large animals.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.