A Compact Computational Model for Hyperthermia-Controlled Drug Release Based on Krogh-Cylinder Approach

Hyperthermia-mediated drug delivery offers a promising strategy to enhance the efficacy of chemotherapy while minimizing systemic toxicity. Thermosensitive liposomes (TSLs) release their therapeutic payload in response to elevated temperature, enabling targeted delivery to tumor tissues. Here we introduce a hybrid multiscale model based on a Krogh cylinder approach to describe temperature-sensitive liposome transport and drug release in tumor tissue. Spatial transport of liposomes and released drug in the vascular and interstitial domains is described by one-dimensional (1D) transport equations, while intracellular drug internalization is represented by local compartmental (0D) kinetics. The model incorporates key physiological processes including blood flow, passive transvascular diffusion of liposomes, interstitial diffusion of released drug, and cellular uptake via receptor binding and internalization. The temperature field is calculated using the Pennes' bioheat equation, and its effects on physiological parameters-such as permeability, diffusivity, and blood velocity-are incorporated via temperature-dependent functions. A sensitivity analysis was performed to identify dominant transport parameters. Microvascular permeability, tissue diffusivity and Krogh cylinder radius were identified as the most influential parameters affecting drug delivery. Simulation results revealed that a 30-min preheating phase prior to drug administration significantly enhances treatment efficacy, increasing internalized doxorubicin concentrations by 29.4% while maintaining a low probability (5%) of tissue necrosis. This compact and computationally efficient model provides an effective framework for designing and optimizing hyperthermia-assisted chemotherapy. Its computational efficiency and physiological detail make it specifically suitable for use in treatment planning and real-time therapeutic decision-making in solid tumors.