A mathematical model for maximizing drug uptake in low-EPR tumors using different methods of ultrasound-mediated drug delivery

Cancer remains a significant health burden and research efforts aim to improve drug delivery options. Focused ultrasound has emerged as a potential mechanism for enhanced targeted drug delivery in tumors with a low Enhanced Permeability and Retention (EPR) effect by “sonoporation”. Traditional sonoporation has shown promise, but it can still benefit from improvements in drug uptake. The current study investigates the use of a new non-portative technique, called “ultrasonic tumor painting,” to enhance vascular retention of nanoparticles in the tumor space to achieve targeted drug delivery and increase therapeutic efficacy. An existing mathematical model was adapted to simulate the concentration of free and liposome encapsulated doxorubicin in circulation. The simulations were performed in MATLAB and specifically evaluate doxorubicin uptake in low EPR tumors. To increase drug uptake, sonoporation was employed where efficiency of intratumoral liposomal doxorubicin uptake was increased. An alternative non-permeabilizing strategy, called “tumor painting,” was utilized to improve vascular retention instead of increasing permeability. After retention, the small molecule doxorubicin is allowed to leak into the tumors space via concentration mediated Fickian Diffusion. This study demonstrates that ultrasound-based drug delivery can be improved with tumor painting. This method is a valuable tool to overcome the limitations of traditional sonoporation and has exciting potential for enhancing the therapeutic efficacy of chemotherapy.