title: Methotrexate-loaded chitosan- and glycol chitosan-based nanoparticles: a promising strategy for the administration of the anticancer drug to brain tumors.
abstract: Brain tumor treatment employing methotrexate (MTX) is limited by the efflux mechanism of Pg-p on the blood-brain barrier. We aimed to investigate MTX-loaded chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the absence of a coating layer of Tween 80 for brain delivery of MTX. The effect of a low Tween 80 concentration was evaluated. MTX NPs were formulated following the ionic gelation technique and size and zeta potential measurements were acquired. Transport across MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma cell line were also performed. Cell/particles interaction was visualized by confocal microscopy. The particles were shown to be cytotoxic against C6 cells line and able to overcome MDCKII-MDR1 cell barrier. GCS-based NPs were the most cytotoxic NPs. Confocal observations highlighted the internalization of Tween 80-coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that even a low concentration of Tween 80 is sufficient for enhancing the transport of MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising strategy for the administration of MTX to brain tumors which merits further investigations under in vivo conditions.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Bari, Italy. atrapani@farmchim.uniba.it
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.forename: Giuliano
authors.initials: G
authors.lastname: Iacobellis
authors.forename: Johannes
authors.initials: J
authors.lastname: Sitterberg
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006018:Glycols / Q000737:chemistry*; D007700:Kinetics; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014162:Transfection
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D006018:Glycols; D011136:Polysorbates; D048271:Chitosan; D008727:Methotrexate