TY - JOUR AU - Yang Hong AU - Liu Zhong-hua AU - Liu Yi-yao AU - Lou Chang-chun AU - Ren Zheng-long AU - Miyoshi Hirokazu PY - 2016 TI - Vascular gene transfer and drug delivery in vitro using low-frequency ultrasound and microbubbles JF - Acta Pharmacologica Sinica; Vol 31, No 4 (April 2010): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: To determine the effects of ultrasound exposure in combination with a microbubble contrast agent (SonoVue) on the cellular uptake and delivery of drugs/genes into human umbilical vein endothelial cells (HUVECs) as well as their biological effects on migration. Methods: HUVECs in suspension were exposed to pulsed ultrasound with a 10% duty cycle in combination with various concentrations of a microbubble contrast agent (SonoVue) using a digital sonifier at a frequency of 20 kHz and an intensity of 3.77 W/cm 2 on the surface of a horn tip. Cell culture inserts were used to determine the cell migration ability. Results: Exposure to pulsed ultrasound resulted in enhanced green fluorescent protein (EGFP) gene transfection efficiencies ranging from 0.2% to 2%. The transfection efficiency of HUVECs was approximately 3-fold higher in the presence of SonoVue than in its absence at the effective exposure time of 6 s. For drug delivery to HUVECs using ultrasound, the delivery efficiencies of a low-molecular-weight model drug (TO-PRO ® −1, M W 645.38) were significantly higher when compared to drug delivery without ultrasound, with a maximum efficiency of approximately 34%. However, the delivery efficiencies of a high-molecular-weight model drug (Dextran-Rhodamine B, M W 70 000) were low, with a maximum delivery efficiency of nearly 0.5%, and gene transfection results were similarly poor. The migration ability of HUVECs exposed to ultrasound was also lower than that of the control (no exposure). Conclusion: The use of low-frequency and low-energy ultrasound in combination with microbubbles could be a potent physical method of increasing drug/gene delivery efficiency. This technique is a promising nonviral approach that can be used in cardiovascular disease therapy. UR - http://www.chinaphar.com/article/view/6699