Numerical modeling of high-intensity focused ultrasound-mediated intraperitoneal delivery of thermosensitive liposomal doxorubicin for cancer chemotherapy

Abstract

Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU). A computational model is developed to evaluate the proposed drug delivery system. Results show an order of magnitude increase in drug penetration depth into the tumor compared to the conventional IP delivery. Furthermore, the effects of thermal conditions applied to the tumor, TSL size, tumor vessel permeability, and tumor size are investigated. Results indicate an improved efficiency of the drug delivery by expanding the heated region, yet, it increases the risk of unintentional TSL drug load release in the peritoneal cavity. Results also indicate that smaller TSLs have better treatment outcome. However, there is a significant reduction in treatment efficacy for TSLs with sizes smaller than the vessel wall pore size. Thus, tuning the size of TSL should be based on the tumor microvascular permeability. The simulation results suggest that the TSL-Dox delivery system in smaller tumors is far advantageous than larger ones. Results of our model can be used as guidelines for future preclinical studies.

Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors

“…This raises the main question in this study that is: Why, unlike other studies 26 that have used MR-HIFU technology, HIFU has not been used for mild hyperthermia? Based on the literature 27 , the authors did not consider HIFU (single-element transducer) to be able to raise the tumor temperature evenly, so in most areas of the tumor, the drug is not released from the carrier. Therefore, in this study, hyperthermia caused by contrast MRI was taken, which is able to increase the tumor temperature relatively uniform.…”

PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment

“…Furthermore, nanoparticles, due to their small size, could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy [14]. In fact, several nanoformulations have been designed for the IP administration of chemotherapeutics [15][16][17] in the treatment of peritoneal metastases due to their higher efficacy compared to their intravenous administration; thus, a higher amount of the drug is expected to reach the tumour. When nanoparticles are intravenously administered, a part of the drug is released and distributed to other tissues before reaching the tumour.…”

Towards principled design of cancer nanomedicine to accelerate clinical translation

“…Ultrasound is of particular importance due to its non-invasive nature and its deeper penetration into tissue. Ultrasound-responsive nanocarriers must be stable so that the enclosure is stable before the arrival of ultrasonic waves but releases its payload upon exposure to the waves [ 323 , 324 ]. Magnetic fields have the ability to generate heat due to the alternating magnetic field for drug release and ablation, besides increasing the accumulation of nanoparticles in tumor tissue [ 325 , 326 ].…”