Abstract

Aim: To explore the nature of hydrogen peroxide at higher dosage for denature-aggregation of tumor with drugs through aggregation in denatured tumor for turning extracellular matrix into autologous coagulum for drug depot and prolong function of drug.

Method: Injection of oxidant mixed drug into tumor.

i. Preparation for two 5 ml of BLM-^I131, one diluted with 0.12 ml NS and 0.2 ml (0.2mCi =49.67μg BLM) for tumor injection in control group; one diluted with 0.12 ml of H₂O₂ (0.833 mg/ml) and 0.2 ml (0.2mCi =49.67μg BLM) for tumor injection in experimental group.
ii. Tumor imaging with BLM-^I131 analyzed at different time points.
iii. Radioactivity in tumor of mice analyzed under SPECT scanning imaging instrument at the 0, 5 h, 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 96 h, 120 h, 144 h and 168 h, activity of isotope ^I131 is representing the BLM retaining time in tumor.
iv. Also, tumor sectioned and observed cellular and extracellular matrix changes of histological structure.

Result: It was observed that BLM-^I131 with ROS in tumors sustained for 168 hours while BLM-^I131 with NS in tumors sustained for 8 hours only. Radioactivity of BLM-^I131 in tumors with ROS reach at peak 1.5 hours and second peak at 20 hours by average to extend to 168 hours, while radioactivity of BLM-^I131 in tumors with NS reached at peak in 0.5 hour, decreased to 30% in 1.5 hour quickly to background in 8 hours; We observed the extracellular matrix changes in experimental tumor while no changes in control tumor.

Conclusion: A water soluble oxidant mixed with free drug can play a biological scissors role to chop tumor matrix, then it resulted in a denature tumor matrix into a coagulation for a drug depot, it showed drug of BLM-^I131 sustained in tumor for a long time; while oxidant plays an important role to punch holes on cell membrane and resulted a high permeability for high concentration drug in each cancer cells.

Keywords: Drug delivery; Extracellular Matrix as Drug Carrier; Autologous Coagulum; Intracellular Drug Delivery