Glioblastoma is known as one of the most aggressive human cancers. To gain access of the brain, therapeutic agents must overcome blood-brain barrier (BBB). In this study, Cisplatin (Cispt)-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared through miniemulsion polymerization technique. They were coated with polysorbate 80 to cross the BBB of glioblastoma-bearing rats. Prepared NPs were characterized with respect to their size, size distribution, zeta potential, drug loading and encapsulation efficiency, cytotoxicity effects, drug release, and stability pattern. Size and zeta potential of nanodrug were found to be 489 nm and -20 mV, while drug loading and encapsulation efficiency were determined to be 5% and 25%, respectively. Release studies demonstrated high retention capability of nanodrug in that 3.18% of Cispt was released from NPs in a period of 51 h. NPs presented acceptable stability after 2 months and lyophilization. Mean survival time in nanodrug receivers was 19.6 days, while it was 17.5 days for free drug receivers. Histological studies demonstrated efficacy of PBCA NPs in reducing side effects. Finally, such preparation can be considered as a promising nanocarrier for other types of tumor.