The treatment of Glioblastoma Xenografts by surfactant conjugated dendritic nanoconjugates

Abstract

Polysorbate 80 (P80) anchored poly(propyleneimine) (PPI) dendritic nanoconjugate was developed and evaluated for targeting anti-cancer drug, docetaxel (DTX) to the brain tumor. In vitro cytotoxicity studies of free DTX, DTX-PPI and DTX-P80-PPI dendrimers were carried out using U87MG human glioblastoma cell line. The in vivo anti-cancer activity in brain tumor bearing rats revealed that DTX loaded P80 conjugated dendrimers reduced the tumor volume extremely significantly (p < 0.0001; more than 50%). The median survival time for brain tumor bearing rats treated with DTX-P80-PPI dendrimers (42 days) was extended very significantly as compared to DTX-PPI (23 days; p < 0.001), receptor blocked group (15 days; p < 0.001) and free DTX (18 days; p < 0.001). Gamma scintigraphy and biodistribution studies further confirmed the targeting efficiency and higher biodistribution of ligand conjugated dendrimer into the brain. The results concluded that the developed nanoconjugate has potential to deliver significantly higher amount of drug to brain tumor for improved therapeutic outcome.