title: The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model.
abstract: There is much interest in utilizing the intrinsic properties of magnetic nanoparticles (MNPs) for the theranostic approaches in medicine. With an aim to develop a potential therapeutics for glioma treatment, efficacy of aqueous dispersible paclitaxel loaded MNPs (Pac-MNPs) were studied in glioblastoma cell line (U-87). The identified potential receptor, glycoprotein non-metastatic melanoma protein B (GPNMB) overexpressed by glioblastoma cells, was actively targeted using GPNMB conjugated Pac-MNPs in U-87 cells. As blood brain barrier (BBB) is the primary impediment in the treatment of glioblastoma, therefore, an attempt was taken to evaluate the biodistribution and brain uptake of Pac-MNPs in rats. The bioavailability of Pac-MNPs illustrated a prolonged blood circulation in vivo, which demonstrated the presence of significant amounts of drug in rat brain tissues as compared to native paclitaxel. Further, the transmission electron microscopy (TEM) study revealed significant accumulation of the Pac-MNPs in the brain tissues. Being an effective contrast enhancement agent for magnetic resonance imaging (MRI) at tissue levels, the MNPs devoid of any surfactant demonstrated enhanced contrast effect in liver and brain imaging. Hence, the significant prevalence of drugs in the rat brain tissues, in vitro targeting potentiality as well as the augmented contrast effect elicit the non-invasive assessment and theranostic applications of MNPs for brain tumor therapy.
authors.affiliation: Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023, Orissa, India.
authors.forename: Fahima
authors.initials: F
authors.lastname: Dilnawaz
authors.forename: Abhalaxmi
authors.initials: A
authors.lastname: Singh
authors.forename: Sujeet
authors.initials: S
authors.lastname: Mewar
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
authors.forename: N R
authors.initials: NR
authors.lastname: Jagannathan
authors.forename: Sanjeeb Kumar
authors.initials: SK
authors.lastname: Sahoo
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D057809:HEK293 Cells; D006207:Half-Life; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D023421:Models, Animal; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013501:Surface-Active Agents / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D003374:Coumarins; D058185:Magnetite Nanoparticles; D008562:Membrane Glycoproteins; D012996:Solutions; D013501:Surface-Active Agents; C030123:coumarin; D017239:Paclitaxel