Background and objectives: Non-aggregated protamine impregnated poly(lactide-co-glycolide) nanoparticles of cisplatin (Pt-PLGA NPs) were synthesized to augment brain delivery. Methods and results: The mean particle size of Pt-PLGA NPs and PLGA NPs were observed to be 173.2 +/- 7.9nm and 140 +/- 10.2 nm, respectively. The Pt-PLGA NPs significantly (p < 50.05, one-way analysis of variance; ANOVA) delivered higher amount (172.41 +/- 15.04 mu g) of cisplatin in comparison to 110.48 +/- 4.71 mu g by PLGA NPs and 20.83 +/- 1.65 mu g by cisplatin solution across in vitro bovine brain microvessel endothelial cells. Cisplatin bearing Pt-PLGA NPs was found to be highly cytotoxic to U87 glioblastoma cells with an IC50 of 2.1 mu M as compared (one-way ANOVA, p < 50.05) to PLGA NPs (3.9 mu M) and cisplatin alone (13.33 mu M). Impregnation with Pt enhanced the uptake of PLGA NPs in U87 glioblastoma cells as compared to PLGA NPs by following endocytosis mechanism. Conclusion: Cisplatin-loaded Pt-PLGA NPs compel preclinical tumour regression study to further improve its utility against glioblastoma.