title: New perspective for the treatment of Alzheimer diseases: liposomal rivastigmine formulations.
abstract: The aim of this study was to determine the transportations of rivastigmine containing from various liposome formulations through Madin Darby Canine Kidney (MDCK) cells monolayer and to compare the in vitro test results with in vivo. There is no other liposome formulation of rivastigmine and the transportations of rivastigmine through MDCK cell monolayers or related study available in the literature. Cytotoxicity (MTT) test was used to determine cell viabilities. The effect of sodium-taurocholate or dimethyl-beta-cyclodextrine as penetration enhancer was also investigated. Characterization and stability studies for liposome formulations were performed. Permeation experiments of rivastigmine were performed through MDCK cells and dialysis membrane. The kinetic of release from liposomes was also investigated. The highest apparent permeability coefficient (log. values) was obtained with sodium-taurocholate liposomes for -1.15 ± 0.16 for MDCK cell. Rivastigmine liposomes and solutions were also administered to mice orally and intraperitonally. Acetylcholinesterase (AChE) activity was determined by Ellman method. AChE% inhibition values were calculated for both blood and brain after administration of rivastigmine solution and liposomes. The highest AChE inhibition was observed for rivastigmine-sodium-taurocholate liposomes. Histological observations of the mice' brains were performed under transmission electron microscope (TEM). The histological results were also indicated and supported all these findings.
authors.affiliation: Department of Pharmaceutical Technology, Gazi University Faculty of Pharmacy, Ankara.
authors.forename: N Başaran
authors.initials: NB
authors.lastname: Mutlu
authors.forename: Zelihagül
authors.initials: Z
authors.lastname: Değim
authors.forename: Şükran
authors.initials: Ş
authors.lastname: Yilmaz
authors.forename: Dinç
authors.initials: D
authors.lastname: Eşsiz
authors.forename: Ahmet
authors.initials: A
authors.lastname: Nacar
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D010316:Particle Size; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068836:Rivastigmine; D013656:Taurocholic Acid / Q000008:administration & dosage; D047392:beta-Cyclodextrins / Q000008:administration & dosage
chemical_list: D002800:Cholinesterase Inhibitors; D004337:Drug Carriers; D008081:Liposomes; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D013656:Taurocholic Acid; D000068836:Rivastigmine