Ultrasound-Targeted Microbubble Destruction Augments Protein Delivery into Testes

Abstract

Objectives Gas-filled microbubbles have become an important tool as ultrasound contrast agents. In recent years, ultrasound-targeted microbubble destruction (UTMD) has evolved into a new tool for organ-specific gene and drug delivery. Although many studies have been performed in well-perfused target organs such as the heart or kidney, no study has yet investigated the feasibility of UTMD for delivery of bioactive substances in the testis. Thus, the aim of this study was to determine whether UTMD is a feasible and safe technique to deliver a reporter protein to the testes. Methods Different groups of rats received 2 μg of luciferase protein at varying protocols. One group received luciferase-loaded microbubbles infused intravenously while ultrasound was applied to the right testis. Another group received luciferase without microbubbles but with ultrasound applied to the right testis. Protein uptake was quantified by luciferase assay. Also, to rule out UTMD-induced damage, the testes were analyzed histologically. Results The testes that received ultrasound and luciferase-loaded microbubbles showed about twofold greater luciferase activity compared with testes without ultrasound or without microbubbles. No hemorrhage or microscopic damage was detected. Conclusions The results of our study have shown that UTMD is a safe and feasible technique to augment delivery of bioactive substances to the testes.