Development of Nanoparticles for Drug Delivery to Brain Tumor: The Effect of Surface Materials on Penetration Into Brain Tissue

Surface-modified poly(D,L-lactic-co-glycolic acid) PLGA nanoparticles (NPs) were fabricated via nano-precipitation for obtaining therapeutic concentration of paclitaxel (PTX) in brain tumor. The cellular uptake and cytotoxicity of NPs were evaluated on C6 glioma cells in vitro, and BALB/c mice were used to study the brain penetration and biodistribution upon intravenous administration. Results showed that by finely tuning nanoprecipitation parameters, PLGA NPs coated with surfactants with a size around 150 nm could provide a sustained release of PTX for > 2 weeks. Surface coatings could increase cellular uptake efficiency when compared with noncoated NPs, and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) showed the most significant enhancement. The in vivo evaluation of TPGS-PLGA NPs showed amplified accumulation (> 800% after 96 h) of PTX in the brain tissue when compared with bare NPs and Taxol (R). Therefore, PLGA-NPs with PLGA-TPGS coating demonstrate a promising approach to efficiently transport PTX across blood-brain barrier in a safer manner, with the advantages of easy formulation, lower production cost, and higher encapsulation efficiency. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.