Aim: The present work investigates the efficacy of Polysorbate 80(P80) coated Kokum butter (KB) solid lipid nanoparticles (P80NvKLNs) for the brain targeted delivery of Nevirapine (Nv). Methods: Solid lipid nanoparticles (SLNs) were prepared by nanoprecipitation technique and evaluated for drug excipient compatibility studies, z- average particle size (nm), zeta potential (mv), percentage drug entrapment efficiency (%EE), surface morphology and in-vitro drug release properties. The in-vivo biodistribution and brain targeting efficiency of nanoparticles were studied in healthy male Wistar rat (150-200 g). Results: P80NvKLNs were found to be smooth surfaced, spherical shaped having average particle size of 177.80 +/- 0.82 nm, zeta potential of -8.91 +/- 4.36 mv and %EE of 31.32 +/- 0.42%. P80NvKLNs remained in blood circulation for 48 h maintaining a sustained release in brain for 24 h (p < 0.05). Conclusion: The study proves the efficacy of Polysorbate 80 coated Kokum butter nanoparticles for brain-targeted delivery of drugs providing ample opportunities for further study.