Ultrasound exposure to enhance the biological action of drugs and the delivery of genes into target cells

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11558106
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Tokyo Medical University (2000-2001); Kyoto University (1999)
• Principal Investigator: MORIYASU Fuminori Tokyo Medical University Medicine Professor, 医学部, 教授 (80191055)
• Co-Investigator(Kenkyū-buntansha): MINE Yositaka Toshiba Corporation Medical Systems Research &Development Center, Specialist, 医用機器技術研究所, 研究員 ; TABATA Yasuhiko Institute For Frontier Medical Sciences, Kyoto University, Professor, 再生医科学研究所, 教授 (50211371)
• Project Period (FY): 1999 – 2001
• Keywords: ultrasound / hepatitis B / hepatitis C / interferon(IFN)

Research Abstract

To develop effective drug and gene delivery strategy, we used ultrasound exposure to enhance the pharmacological activity of various drugs. First, we used this method for the treatment of chronic viral hepatitis with interferon (IFN). Although IFN alpha and beta arecurrently recognized as the most effective agents for treating patients with chronic hepatitis B and C, they are well known to cause various adverseeffects. To reduce the dose of IFN necessary for treatment, we tried enhancing the effects of IFN in the liver by ultrasound exposure. Percutaneous insonation in mouse liver following IFN-beta injection with the ultrasound power level used at clinical diagnosis enhanced the IFN-beta-inducedincrease of 2,5-oligoadenylate synthetase (2-5AS) levels in the liver. This enhancement of the 2-5AS level was dependent on the duration as well as on the timing of insonation after the IFN-beta injection. In contrast, liver insonation did not enhance 2-5AS levels in the lung or spleen, and moreover, it did not alter tissue distribution of injected IFN. Thus,the combination of IFN-beta administration and subsequent liver insonation appears to be a promising method for enhancing the antiviral activity of IFN specifically in the liveir, enabling a reduction in the dose necessary for treatment. This technology could be used in clinical setting near future.