Increased Numbers of Injections of Doxorubicin Bound to Nanoparticles Lead to Enhanced Efficacy Against Rat Glioblastoma 101/8

Previous investigations have shown that doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (Tween^® 80) is able to cross the blood-brain barrier upon intravenous administration and is effective against intracranially implanted 101/8 glioblastoma multiforme in rats at the treatment regimen of 3 × 1.5 mg/kg (as doxorubicin) on days 2, 5, 8 post tumour implantation. The objective of the present study was to investigate the possibility to further prolong the survival of rats with 101/8 glioblastoma by extending the treatment regimen. Doxorubicin-loaded poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 were injected using two different therapeutic regimens. Two groups received four injections at the dose of 1.5 mg/kg (as doxorubicin) on days 2, 5, 8, and 16 post tumour implantation and two other groups received an additional injection on day 20 (5 × 1.5 mg/kg). Histological and immunohistochemical analyses were carried out 24 and 30 days after tumour inoculation to assess the effect of the different therapy regimens in comparison to an untreated control group. The results demonstrate that the extended chemotherapy provided an enhanced survival. Comparison of the treatment outcomes revealed that the five-injection regimen produced a more distinctive antitumor effect manifested as a decreased tumour area and proliferation index as well as a decreased necrotic area and a smaller vascular network. Tumour regression was achieved in approximately 40% of the treated animals. These results demonstrate the promising therapeutic potential of doxorubicin-loaded nanoparticles for systemic chemotherapy of human glioblastoma multiforme.