Brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles for brain cancers. (June 2015)

• Record Type: Journal Article
• Authors: Geldenhuys, Werner; Wehrung, Daniel; Groshev, Anastasia; Hirani, Anjali; Sutariya, Vijaykumar
• Is Part Of: Pharmaceutical development and technology. Volume 20:Number 4(2015)
• Page Start: 497
• Page End: 506
• Publication Date: 2015-06
• Subjects: Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.3109/10837450.2014.892130
• Languages: English
• ISSNs: 1083-7450

Abstract

<abstract> <title>Abstract</title> <p> <italic>Objectives</italic>: To prepare and characterize <italic>in vitro</italic> a novel brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles (NPs) for the treatment of brain cancer.</p> <p> <italic>Methods</italic>: Doxorubicin-loaded NPs were prepared by the nanoprecipitation method using PLGA-COOH (<sc>dl</sc>-lactide-<italic>co</italic>-glycolide). The NPs were coated with a glutathione-PEG conjugate (PEG-GSH) in order to target delivery to the brain. The NPs were characterized via <italic>in vitro</italic> studies to determine particle size, drug release, cellular uptake, immunofluorescence study, cytotoxic assay, and <italic>in vitro</italic> blood–brain barrier (BBB) assay.</p> <p> <italic>Results</italic>: The NPs showed a particle size suitable for BBB permeation (particle size around 200 nm). The <italic>in vitro</italic> release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 96 h. The immunofluorescence study showed the glutathione coating does not interfere with the drug release. Furthermore, <italic>in vitro</italic> BBB Transwell™ study showed significantly higher permeation of the doxorubicin-loaded NPs compared with the free doxorubicin solution through the coculture of rat brain endothelial (RBE4) and C6 astrocytoma cells (<italic>p</italic> < 0.05).</p> <p> <italic>Conclusions</italic>: We conclude that the initial <italic>in vitro</italic> characterization of the NPs demonstrates potential in delivering doxorubicin to cancer cells with possible future application in targeting brain cancers <italic>in vivo</italic>.</p> </abstract>