Image-based multiphysics modelling of thermosensitive liposome-mediated drug delivery to liver tumour under high-intensity focused ultrasound heating

• Multiphysics modelling of TSL-mediated drug delivery coupled with HIFU heating. • Performance assessment: fluorouracil, cisplatin, doxorubicin, and paclitaxel. • Drug transport mechanisms in the liver tumour and surrounding tissues. Thermosensitive liposomes combined with high-intensity focused ultrasound provide a promising approach for actively controlled, localised drug delivery. While various cytotoxic drugs have been successfully encapsulated in thermosensitive liposomes, their transport mechanisms and overall performance remain poorly understood, limiting the clinical advancement of this combination therapy. This study applies multiphysics modelling to a 3-D liver tumour model reconstructed from patient magnetic resonance images to evaluate the performance of four commonly used cytotoxic drugs, including fluorouracil, cisplatin, doxorubicin, and paclitaxel, under identical delivery conditions. The results demonstrate the effectiveness of this combination therapy in enhancing drug accumulation within the tumour while minimising drug exposure to surrounding tissues, thereby reducing the risk of side effects. Quantitative analysis reveals that tumour drug accumulation is primarily governed by a balance between local drug release from thermosensitive liposomes, drug exchange between tissue plasma and tissue extracellular space, and drug elimination. In contrast, lymphatic drainage replaces drug release as one of the key factors, alongside the other two mechanisms, in determining drug concentrations in surrounding tissues. Cross-comparisons highlight the significant impact of drug-specific properties on transport behaviour. Paclitaxel shows the poorest delivery efficacy due to low vascular permeability. Cisplatin results in the highest drug exposure in both tumour and non-tumour tissues. Doxorubicin leads to a comparable risk of side effects with a lower tumour accumulation. Conversely, fluorouracil, despite its rapid concentration changes, achieves effective tumour delivery while reducing drug exposure in surrounding tissue. These findings provide valuable insights for drug selection and development of this combination therapy.