Open Access

Telli Hekmatara

• Many highly active antitumour agents are currently not employable for the systemic chemotherapy of brain tumours since their entrance into the brain is blocked by the BBB. Obviously, the development of a strategy allowing effective delivery of these agents across the BBB would enormously extend the potential of the systemic chemotherapy. Chemotherapy of rat glioblastoma using nanoparticle-bound doxorubicin Doxorubicin bound to polysorbate-coated nanoparticles had been previously shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. The objective of this study was to investigate the therapeutic effects of this formulation by morphometric, histological and immunohistological methods. The 101/8 glioblastoma was implanted intracranially into the male Wistar rats. The animals were randomly divided into 3 groups; one group served as untreated control (n = 20). The second group received doxorubicin in solution (Dox-sol, n = 18), and the third group received doxorubicin bound to PBCA nanoparticles coated with PS 80 (Dox-NP + PS 80, n = 18). The treatment regimen was 3 × 1.5 mg/kg on days 2, 5, and 8 after tumor implantation. The formulations were injected into the tail vein. The untreated control animals were sacrificed on days 6, 8, 10, 12, and 14 after the implantation. The animals that had received chemotherapy were sacrificed on day 10, 14 and 18 after the implantation. The brains were investigated by morphometrical, histochemical, and immunohistochemical methods such as the measurement of the tumor size, proliferation of tumor cells, vessel density, expression of glial fibrillary acidic protein (GFAP), expression of vascular endothelial growth factor (VEGF), incidence and dimension of necrosis, and microvascular proliferation. Tumours showed signs of malignancy including invasion to brain tissue and brisk mitotic activity. The tumor proliferation remained stable at high levels throughout the host survival time. Overall, the tumor showed a reproducible growth pattern and temporal development that is comparable to human glioblastoma. Furthermore, the 101/8 glioblastoma had infiltrated diffusely the surrounding host brain at the edge of the solid tumor mass showed no signs of encapsulation. Thus the 101/8 glioblastoma fulfills the most criteria for an adequate glioma model and can be qualified as a reliable model. ...
• Viele hochaktive Zytostatika sind zurzeit für die systematische chemotherapeutische Anwendung nicht einsetzbar, weil ihr Eintritt ins Gehirn durch die Blut-Hirn-Schranke (BHS) blockiert wird. Die Entwicklung einer Möglichkeit zum Transport dieser Stoffe über diese Schranke würde das Potenzial einer systemischen Chemotherapie bedeutend erhöhen. Chemotherapie von Glioblastomen mit Doxorobicin beladenen Nanopartikeln In früheren Studien wurde gezeigt, dass die Überlebenszeiten von Ratten mit ins Gehirn transplantierten 101/8 Glioblastomen durch mit Polysorbat 80 überzogenen Doxorubicin-Nanopartikel signifikant verlängert werden können. Ziel der vorliegenden Studie war es, die Effizienz dieser Doxorubicin-beladenen Nanopartikel mit morphometrischen, histologischen und immunohistologischen Methoden zu untersuchen, um so die Tiere weniger zu belasten als das in Letalitätsstudien erfolgt. Das 101/8 Glioblastom wurde dazu intrakranial männlichen Wistar-Ratten implantiert. Die Ratten wurden randomisiert in drei Gruppen geteilt: die erste Gruppe erhielt keine Behandlung (Kontrolle, n = 20), die zweite Gruppe wurde mit Doxorubicin-Lösung (Dox-sol, n = 18) und die dritte Gruppe mit Polysorbat 80-überzogenen Doxorubicin-Nanopartikeln (Dox-NP + PS 80, n = 18) behandelt. ...