At each time point, rabbits have been euthanized below deep anesthesia by slow intravenous injection of the lethal dose of sodium pentobarbital. Samples through the tumor, peritumoral liver parenchyma, and nontargeted liver tissues inside the left and right lobe had been obtained. These tissue samples were placed within a dry ice container instantly right after preparation and frozen at 80C right up until the time of evaluation. Doxorubicin concentration analysis was performed by means of atomic absorption spectroscopy. Pieces through the tumor core, tumor periphery, and peritumoral surrounding liver parenchyma have been stained with H&E and sent for pathologic examination. Tumor necrosis as seen with H&E on pathology slides was estimated using a freeware image analysis program . The in vitro experiment showed 82¨C94% maximal doxorubicin loadability into the QSMs at 2 h and 6% doxorubicin release within the first 6 h, followed by a slow drug release pattern . All implanted Vx-2 tumors had been grown successfully during the liver, with a mean axial diameter of 3.
0 cm , measured on pathology. A sufficient tumor size and hypertrophic tumor feeding artery allowed the selective arteriography in all rabbits, and selective delivery of the whole amount of doxorubicin-loaded QSM was possible. In our study, the highest doxorubicin plasma concentration was noted at 20 min immediately after treatment , which subsequently selleck more hints dropped over time . Of note, doxorubicin levels have been not measured between 0 and 19 min following injection, since the 20-min time point was our initial one. High intratumoral doxorubicin concentrations were recorded during the first 3 days following treatment . At 7 days following treatment , intratumoral doxorubicin concentration dropped to 23.1372 nM/ g. The percentage drug concentration from the peritumoral liver parenchyma ranged from 5.6% to 6.
2% of the intratumoral concentration. Doxorubicin concentrations from the nontargeted left and appropriate lobe of the liver have been undetectable . Upon histopathology, an initial burst of tumor necrosis was observed at 3 days and a pronounced 90% tumor killing effect was achieved at 7 days just after treatment with doxorubicinloaded QSMs. At 7 days, the control group achieved from this source 60% tumor necrosis . Of note, the Vx-2 tumor model is notorious for being necrotic at baseline, and according to our experience, a 40% tumor necrosis was expected and taken into account when comparing groups . The intratumoral presence of doxorubicin-loaded QSMs was well demonstrated in all rabbits . In this animal study, we utilized poly copolymer microspheres , which have the unique feature of proportionally expanding in size when in aqueous solution.
Moreover, this material is a negatively charged polymer and may interact with positively charged drugs, such as doxorubicin. Our in vitro experiment demonstrated a high doxorubicin loadability and sustained drug release over time.