In Vivo Sonoporation Effect Under the Presence of a Large Amount of Micro-Nano Bubbles in Swine Liver

Abstract

Objectives Sonoporation as a method of intracellular drug and gene delivery has not yet progressed to being used in vivo. The aim of this study was to prove the feasibility of sonoporation at a level practical for use in vivo by using a large amount of carbon dioxide micro-nano bubbles. Methods The carbon dioxide micro-nano bubbles and 100 mg of cisplatin were intra-arterially injected to the swine livers, and ultrasound irradiation was performed from the surface of the liver under laparotomy during the intra-arterial injection. After the intra-arterial injection, ultrasound-irradiated and nonirradiated liver tissues were immediately excised. Tissue platinum concentration was measured using inductively coupled plasma mass spectrometry. Liver tissue platinum concentrations were compared between the irradiated tissue and nonirradiated tissue using the Wilcoxon signed rank test. Results The mean (SD) liver tissue platinum concentration was 6.260*103 (2.070) ng/g in the irradiated liver tissue and 3.280*103 (0.430) ng/g in the nonirradiated liver tissue, showing significantly higher concentrations in the irradiated tissue (P = 0.004). Conclusions In conclusion, increasing the tissue concentration of administered cisplatin in the livers of living swine through the effect of sonoporation was possible in the presence of a large amount of micro-nano bubbles.