Enabling Microparticle Imprinting to Achieve Penetration and Local Endurance in the Peritoneum via High-Intensity Ultrasound (HIUS) for the Treatment of Peritoneal Metastasis

Abstract

Introduction. Micro- and nanoparticles, with their submicron size, the versatility of physical and chemical properties, and easily modifiable surface, are uniquely positioned to bypass the body’s clearing systems. Nonetheless, two main problems with micro- and nanoparticles arise which limit the intraperitoneal application. The study was performed to evaluate whether HIUS enables the imprinting of microparticles and, therefore, enhances penetration and local endurance in the peritoneum. Methods. High-intensity ultrasound (HIUS) at 20 kilohertz with an output power of 70 W was applied on peritoneal tissue samples from fresh postmortem swine for different time intervals. Before the HIUS application, the surface of the samples was covered with strontium aluminate microparticles before analysis via electron microscopy. In-tissue strontium aluminate penetration and particle distribution size were measured using fluorescence microscopy on frozen thin sections. Results. With increasing HIUS durations (1 versus 5 minutes), increasing strontium aluminate particles were detected in the peritoneum. HIUS leads to a particle selection process with enhancing predominantly the penetration of smaller particles whereas larger particles had a harder time penetrating the peritoneum. Smaller particles were detected up to 277 µm ± 86 µm into the peritoneum. Conclusion. Our data indicate that HIUS might be used as a method to prepare the peritoneal tissue for micro- and nanoparticles. Higher tissue penetration rates without the increase and longer local endurance of the applied substance could be reached. More studies need to be performed to analyze the effect of HIUS in enhancing intraperitoneal drug applications.