At each time level, rabbits had been euthanized underneath deep anesthesia by slow intravenous injection of a lethal dose of sodium pentobarbital. Samples in the tumor, peritumoral liver parenchyma, and nontargeted liver tissues during the left and right lobe were obtained. These tissue samples have been placed in the dry ice container right away soon after preparation and frozen at 80C right up until the time of examination. Doxorubicin concentration examination was performed through atomic absorption spectroscopy. Pieces from the tumor core, tumor periphery, and peritumoral surrounding liver parenchyma have been stained with H&E and sent for pathologic analysis. 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 were grown successfully inside 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 soon after treatment , which subsequently selleck chemical the full details dropped over time . Of note, doxorubicin levels have been not measured between 0 and 19 min after 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 within the peritumoral liver parenchyma ranged from 5.6% to 6.
2% of the intratumoral concentration. Doxorubicin concentrations from the nontargeted left and ideal lobe of the liver were 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 following treatment with doxorubicinloaded QSMs. At 7 days, the control group achieved selleckchem straight from the 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.