Spatio-temporal investigation of doxorubicin in a 3D heterogeneous tumor microenvironment

Doxorubicin (Adriamycin) is a type of chemotherapy drugs using to treat diseases such as breast cancer, bladder cancer, Kaposi's sarcoma, and lymphoma. Additionally, it can be first prescribed to reduce tumor size. The ratio of killed cells is varied depending on the clinical dosage regimen. Hence, the exact dosage of the drug must be administered to prevent the toxicity that could impair the immune system or leading to heart failure. In the present study, a 3D heterogeneous geometry with a solid tumor and healthy tissue is modeled for the drug delivery investigation. At the first stage, the physical properties of tumor microenvironment are obtained. Then, a five-compartmental model is used to evaluate the free, bound and internalized drug via the convection-diffusion-reaction (CDR) equation. Results are shown that a percent increase of 37.5% and 47.1% for the 75 mg m^-2 to 50 mg m^-2 in the AUC of bound drug and free drug concentration, respectively. The free and bound drugs have the same trend in time showing an apex at the earliest time of injection and then drops to the lowest amount about 9 hours after treatment. Moreover, the internalized drug has a different trend in time. It increases and reaches a constant amount of drug concentration in the cells. Besides, the fraction of surviving cells is also evaluated for both tumor and healthy tissues showing a 88.62% and 97.76% of surviving cells with 50 mg m^-2 of doxorubicin after the treatment, respectively. This model is developed to predict the heterogenous distribution of doxorubicin in three different drug concentrations for patient-specific drug treatment. This model could be used for different drugs to show the rate of perfusion and the ability to kill cancerous cells regarding their different doses and toxicity effects.