Drug-Induced Pathomorphosis of Glioblastoma 101.8 in Wistar Rats Treated with Doxorubicin Bound to Poly(lactide-co-glycolide) Nanoparticles

The aim of the investigation was to study drug-induced pathomorphosis of glioblastoma 101.8 in Wistar rats treated with different doxorubicin formulations: doxorubicin bound to polylactide nanoparticles and doxorubicin substance.

Materials and Methods. Doxorubicin bound to poly(lactic-co-glycolic acid) (PLGA) nanoparticles was used in the investigation. The study was performed on 33 male Wistar rats receiving doxorubicin (DOX) substance or doxorubicin-loaded nanoparticles (DOX-PLGA) at a dose of 1.5 mg/kg (body weight) on days 2, 5, and 8 post tumor transplantation. Lyophilized nanoparticles were resuspended in water (DOX-PLGA) or in 1% aqueous solution of poloxamer 188 (DOX-PLGA/P188) before intravenous administration. The number of mitotically dividing and dying tumor cells was counted, and the tumor cell renewal coefficient (CRC) was calculated for evaluation of pathomorphosis of glioblastoma 101.8 induced by doxorubicin, on day 14 post transplantation. The number and volume fraction of blood vessels in tumors were determined on histological sections stained with isolectin B4.

Results. On day 6 post treatment, the tumors in rats treated with all doxorubicin formulations exhibited an increase of cell death rate, decreased proliferative activity, and a lower indicator of CRC of tumor cells, compared to untreated animals. A decrease in the volume fraction and number of blood vessels in the tumors was also observed in the animals subjected to chemotherapy. According to the tumor pathomorphism parameters assessed in this study, the most effective formulation was DOX-PLGA/P188.

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Fedoseeva V.V., Postovalova E.A., Khalansky A.S., Razzhivina V.A., Gelperina S.E., Makarova O.V. Drug-Induced Pathomorphosis of Glioblastoma 101.8 in Wistar Rats Treated with Doxorubicin Bound to Poly(lactide-co-glycolide) Nanoparticles. Sovremennye tehnologii v medicine 2018; 10(4): 105, https://doi.org/10.17691/stm2018.10.4.12