title: Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for brain cancer.
abstract: Gliomas are some of the most aggressive types of cancers but the blood-brain barrier acts as an obstacle to therapeutic intervention in brain-related diseases. The blood-brain barrier blocks the permeation of potentially toxic compounds into neural tissue through the interactions of brain endothelial cells with glial cells (astrocytes and pericytes) which induce the formation of tight junctions in endothelial cells lining the blood capillaries. In the present study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA nanoparticle, show its in vitro drug release data along with cytotoxicity data in C6 and RG2 cells, and investigate its trans-blood-brain barrier permeation through the establishment of a Transwell cellular co-culture. We show that the docetaxel-loaded nanoparticle's size enables its trans-blood-brain barrier permeation; the nanoparticle exhibits a steady, sustained release of docetaxel; the drug is able to induce cell death in glioma models; and the glutathione-coated nanoparticle is able to permeate through the Transwell in vitro blood-brain barrier model.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd. MDC 30, Tampa, Florida, 33612-4749, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Grover
authors.forename: Anjali
authors.initials: A
authors.lastname: Hirani
authors.forename: Yashwant
authors.initials: Y
authors.lastname: Pathak
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Sutariya
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D018920:Coculture Techniques; D003692:Delayed-Action Preparations; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D017097:Electric Impedance; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D050997:Nanomedicine; D053758:Nanoparticles; D010539:Permeability; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D043823:Taxoids; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D000077143:Docetaxel; D011092:Polyethylene Glycols; D005978:Glutathione