Computational models have been developed as a potential platform to identify bio-interactions that cannot be properly understood by experimental models. In the present study, a mathematical model has been employed to investigate the therapeutic response of drug-loaded thermosensitive liposome (TSL) following intravascular release paradigm. Thermal field created by an alternating magnetic field is utilized to release the drug within microvessels. Determining the time required for the application of magneto-hyperthermia is the main purpose of this study. Results show that applying a long-term continuous or pulsed hyperthermia can affect the concentration level of drugs in the extracellular space. The peak value of free and bound drug concentrations in the extracellular space is equal for all hyperthermia programs. Additionally, the concentrations of free and bound drugs are retained at a higher level in pulsed mode compared to the continuous mode (i.e., area under curve (AUC) of pulsed case is slightly higher than continuous case). However, there is no significant difference in bioavailability time. Hence, onset time of tumor growth is similar for different conditions. This study shows that the appropriate time to apply hyperthermia is post-bolus injection until reaching the peak concentration profile in extracellular space. Therefore, in clinical applications similar to the present study's circumstances, continuous hyperthermia for 30 min can be a better choice. This study can be a useful guideline for experimental studies to reduce the number of in vivo tests as well as for clinical trials to make the right decision to provide optimal medication programs.
Keywords: alternating magnetic field; cancer nanomedicine; hyperthermia; targeted drug delivery; thermo-sensitive liposome.
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