Abstract
Systemic toxicity and insufficient drug accumulation at the tumour site are main barriers in chemotherapy. Thermosensitive liposomes (TSL) combined with high intensity focused ultrasound (HIFU) has emerged as a potential solution to overcome these barriers through targeted drug delivery and localised release. Owing to the multiple physical and biochemical processes involved in this combination therapy, mathematical modelling becomes an indispensable tool for detailed analysis of the transport processes and prediction of tumour drug uptake. To this end, a multiphysics model has been developed to simulate the transport of chemotherapy drugs delivered through a combined HIFU–TSL system. All key delivery processes are considered in the model; these include interstitial fluid flow, HIFU acoustics, bioheat transfer, drug release and transport, as well as tumour drug uptake. The capability of the model is demonstrated through its application to a 2-D prostate tumour model reconstructed from magnetic resonance images. Our results not only demonstrate the feasibility of the model to simulate this combination therapy, but also confirm the advantage of HIFU–TSL drug delivery system with enhancement of drug accumulation in tumour regions and reduction of drug availability in normal tissue. This multiphysics modelling framework can serve as a useful tool to assist in the design of HIFU–TSL drug delivery systems and treatment regimen for improved anticancer efficacy.Graphical abstract
Highlights
Numerous anticancer drugs have been developed with significant cytotoxicity observed in preclinical studies, but their clinical applications are limited for various reasons
The aim of the present study is to develop a multiphysics model for Thermosensitive liposome (TSL)-mediated drug delivery combined with high intensity focused ultrasound (HIFU) heating
This is because drug migration by convection is determined by the interstitial fluid velocity (IFV), while pressure gradient across the vessel wall directly influences the transvascular exchange of fluid and drugs
Summary
Numerous anticancer drugs have been developed with significant cytotoxicity observed in preclinical studies, but their clinical applications are limited for various reasons Among these poor treatment efficacy and systemic toxicity are the main obstacles for effective chemotherapy in patients. Thermosensitive liposome (TSL) combined with high intensity focused ultrasound (HIFU) offers a promising drug delivery system to overcome the limitations of conventional chemotherapy through actively targeted and triggered release of drugs at the tumour site. With this delivery system, drug-loaded TSL are intravenously administrated and circulate with bloodstream to reach the tumour site. There is still a lack of understanding on the drug transport mechanism and tumour drug uptake in response to temperature variation upon HIFU heating
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