title: Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo.
abstract: A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.
authors: Resham
authors: R
authors: Chhabra
authors: Barbara
authors: B
authors: Ruozi
authors: Antonietta
authors: A
authors: Vilella
authors: Daniela
authors: D
authors: Belletti
authors: Katharina
authors: K
authors: Mangus
authors: Stefanie
authors: S
authors: Pfaender
authors: Tasnuva
authors: T
authors: Sarowar
authors: Tobias Maria
authors: TM
authors: Boeckers
authors: Michele
authors: M
authors: Zoli
authors: Flavio
authors: F
authors: Forni
authors: Maria Angela
authors: MA
authors: Vandelli
authors: Giovanni
authors: G
authors: Tosi
authors: WG Molecular Analysis of Synaptopathies, Neurology Dept., Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. andreas.grabrucker@uni-ulm.de.
authors: Andreas Martin
authors: AM
authors: Grabrucker
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002413:Cations, Divalent / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D006020:Glycopeptides / Q000737:chemistry / Q000633:toxicity; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015032:Zinc / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D002413:Cations, Divalent; D002491:Central Nervous System Agents; D004337:Drug Carriers; D006020:Glycopeptides; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015032:Zinc