title: Investigation of liposome formulation effects on rivastigmine transport through human colonic adenocarcinoma cell line (CACO-2).
abstract: Transportations of rivastigmine containing liposomes across Caco-2 cells were studied and in vitro test results were compared with in vivo results. MTT test was used for cell viability studies. Series of formulations were prepared containing rivastigmine which is used for the treatment of Alzheimer's disease. Characterization and stability studies for liposome formulations were performed. Encapsulation efficiencies of liposomes were 35.4%, 25.2% and 29.9% for rivastigmine, rivastigmine-sodium taurocholate, rivastigmine-dimethyl-beta-CD liposomes, respectively. In stability studies, particle size and size distribution, zeta potential, rivastigmine amounts were determined and shelf lives of liposomes were calculated. Penetration properties of rivastigmine through Caco-2 cells, dialysis membrane and kinetics of release from liposomes were determined. Permeability coefficients were calculated after diffusion studies. The highest value of % cumulative amount of rivastigmine passed through caco-2 cell cultures was found to be 87.2% for rivastigmine-sodium taurocholate solution and 12.8% for rivastigmine-sodium taurocholate liposome. The highest permeability coefficient value was obtained with sodium taurocholate liposomes for -0.75. Rivastigmine liposomes and solutions were also applied to animals. Acetyl choline esterase (AChE) activity was determined by the Ellman method on mice. %AChE inhibition values were calculated using blood and brain tissue samples. The physical appearances of the brains were investigated by TEM microscope. The highest value of AChE inhibition was observed for rivastigmine and sodium taurocholate liposomes. The histological investigations and observations also supported these results.
authors.affiliation: Department of Pharmaceutical Technology, Gazi University Faculty of Pharmacy, Ankara, Turkey. zdegim@gazi.edu.tr
authors.forename: Z
authors.initials: Z
authors.lastname: Degim
authors.forename: N B
authors.initials: NB
authors.lastname: Mutlu
authors.forename: S
authors.initials: S
authors.lastname: Yilmaz
authors.forename: D
authors.initials: D
authors.lastname: Eşsiz
authors.forename: A
authors.initials: A
authors.lastname: Nacar
mesh_terms: D000042:Absorption; D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D005079:Excipients; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D048448:Phenylcarbamates / Q000493:pharmacokinetics*; D000068836:Rivastigmine; D013656:Taurocholic Acid / Q000737:chemistry; D047392:beta-Cyclodextrins
chemical_list: D002800:Cholinesterase Inhibitors; D005079:Excipients; D008081:Liposomes; D048448:Phenylcarbamates; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D013656:Taurocholic Acid; D000068836:Rivastigmine