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.

In-vivo thermodynamic exploration of gas-based intraperitoneal hyperthermia

“…These efforts include attempts to apply new physical principles to the already existing pharmacological options to enhance local antitumoral effects ( 25 – 29 ). Some of these concepts include irradiation ( 30 – 32 ), high-intensity ultrasound ( 33 – 35 ), nanoparticles ( 36 ) as well as the application of new substances ( 37 , 38 ). Hyperthermia notably impacts PM management as it demonstrates great efficacy in enhancing antitumoral effects when combined with chemotherapy or radiation, without causing disproportionate additional side effects ( 39 – 41 ).…”

Evaluating the concept of gas‑based intraperitoneal hyperthermia beyond 43˚C in the treatment of peritoneal metastasis: A pilot study

“…The concept of applying new physical principles and incorporating them into treatments for peritoneal metastases (PM) (15,16) and other surface malignancies (17)(18)(19) has been promising. Many concepts including irradiation (20)(21)(22), high-intensity ultrasound (23)(24)(25) and nanoparticles (26) or new substances (27,28) have been previously investigated for potential clinical use. Beside radiation, hyperthermia is probably the second most widely applied physical principle which is added to chemotherapeutic procedures.…”

Case Report: Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Application in Intraperitoneally Disseminated Inflammatory Myofibroblastic Tumor and in the Youngest Patient in the World: New Indication and Modification of Technique

“…Intraperitoneal chemotherapy ensures a high concentration of the drug in the peritoneal cavity and reduces its systemic side effects. It should be emphasized that the macroscopic excision of all visible lesions (CRS) is crucial for the positive effect of the therapy due to the limited penetration of cytotoxic drugs into the tissues (∼1 mm) (31). The time from surgery to administration of peritoneal chemotherapy is also important.…”