Article Text
Abstract
Introduction Our objective was to demonstrate the safety and efficacy of an ablation-based drug delivery method using ethyl-cellulose ethanol (ECE) through a biodistribution study looking at chemotherapy concentrations in the heart, kidney, liver, lung, spleen, and tumor, as well as a long term survival study in a murine model of breast cancer.
Methods Biodistribution study: 4T1-Luc murine breast tumors were established in female BALB/c mice randomized to one of three groups (n=10 mice per group): ECE + local doxorubicin, ECE + systemic doxorubicin, or saline injection (no ECE) alone. Organ tissue was collected 4 hours after treatment and homogenized for analysis with IVIS imaging to quantify fluorescence from doxorubicin. Survival: 4T1-Luc bearing mice were randomized ECE with local doxorubicin or one of seven control groups (n=~10 mice per group).
Results Figure 1A-C shows the results from the biodistribution study. There were no significant differences in doxorubicin fluorescence within the heart, kidney, liver, and spleen; however, there was a significant increase in doxorubicin fluorescence within the lungs from mice treated with ECE + systemic doxorubicin. Further, there was a significant increase in doxorubicin fluorescence within the tumors of mice treated with ECE + local doxorubicin compared to ECE + systemic doxorubicin and saline control. Figure 1D-F shows the results from the suvival study. Overall survival for ECE + local doxorubicin was significantly longer than treatment with the same doxorubicin dose delivered systemically or locally.
Conclusion/Implications Chemotherapy-loaded ECE reduces systemic chemotherapeutic distribution and increases chemotherapy concentration within the tumor, translating into delayed tumor growth and improved overall survival.