Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)

Abstract

Background. High-intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. is treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. is study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.

Lugol’s Iodine-Enhanced Micro-CT: A Potential 3-D Imaging Method for Detecting Tongue Squamous Cell Carcinoma Specimens in Surgery

“…In addition to temperature, ultrasound also improves the motion and diffusion of molecules. Khosrawipour et al found that, after 300 s of high-intensity ultrasound (HIUS) treatment, tissue penetration of doxorubicin into the peritoneal tissue improved by 3.8-fold (36). Further studies are thus needed to promote the application of I 2 -IK-enhanced micro-CT imaging intraoperatively.…”

Intraperitoneal chemotherapy of the peritoneal surface using high-intensity ultrasound (HIUS): investigation of technical feasibility, safety and possible limitations

“…However, we know that increasing tissue penetration enhances the antitumor effect with a higher local drug disposition [1]. In previous studies, HIUS has demonstrated substantially enhanced drug penetration in the peritoneal tissue [18]. In the clinical setting, HIUS is increasingly used as a non-invasive treatment for both primary and metastatic tumors.…”

“…Thus, there is a pressing need to develop methods with improved drug delivery resulting in increased drug penetration depths. Preliminary data on high-intensity ultrasound (HIUS) are promising and indicate its potential to increase in-depth tissue penetration of applied substances 18 . While the addition of HIUS results in a threefold increased drug penetration compared to conventional IPC without HIUS, the feasibility of its application within the abdominal cavity remains unclear.…”

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

“…HIUS could also activate the particles itself to interact with the surrounding surface and release their chemical compounds as recently shown [13]. e possibility of using HIUS to improve drug penetration of fluid chemotherapy has already been demonstrated [22].…”

“…HIUS could also activate the particles itself to interact with the surrounding surface and release their chemical compounds as recently shown [ 13 ]. The possibility of using HIUS to improve drug penetration of fluid chemotherapy has already been demonstrated [ 22 ]. This effect is supposedly attributed to the morphological changes on the peritoneal surface and on the underlying tissue by HIUS [ 23 ].…”