Acoustic streaming and thermosensitive liposomes for drug delivery into hepatocellular carcinoma tumor adjacent to major hepatic veins; an acoustics-thermal-fluid-mass transport coupling model

While researchers have focused on thermal ablation techniques for the treatment of hepatocellular carcinoma tumors for patients who are not candidates for surgical resection, the treatment is still challenging because of disease recurrence after thermal ablation treatment, particularly for tumors that are close to the major blood vessels of liver. Meanwhile, chemotherapy has received less attention because of its low efficacy and adverse side effects. Herein, using an acoustics-thermal-fluid-mass transport coupling model, we present a novel drug delivery system based on the use of acoustic waves and temperature-sensitive liposomes (TSL). Simulation involves solving the acoustic, bioheat, fluid flow and mass transfer equations. The acoustic streaming effect is also considered in this modeling. The main idea behind the proposed system is the simultaneous use of thermal and hydrodynamic effects of acoustic waves for drug delivery in a TSL-based system. HIFU-induced mild hyperthermia allows drug release and acoustic streaming pushes TSL particles from the vessel wall to the target area. To investigate the effects of using acoustics and liposomes, four different systems, including without-acousticwithout-liposome, with-acoustic-without-liposome, without-acoustic-with-liposome and with-acoustic-withliposome, have been studied. Also, the effect of TSL particle size and acoustic frequency has been investigated. We found that a with-acoustic-with-liposome system can achieve targeted drug delivery by reducing chemotherapy adverse side effects and enhancing drug delivery to the target area. The results show that using such a system, the effective drug penetration into the tissue increased by 56% compared to conventional drug delivery. In addition, the results of the parametric study show that increasing the acoustic frequency in this method results in improved drug delivery. The study of TSL size also indicates that for TSL particles with the same drug-carrying capacity, smaller TSLs perform better.