title: Ligand-functionalized nanoliposomes for targeted delivery of galantamine.
abstract: The purpose of this study was to design ligand-functionalized nanoliposomes that are proficient in providing effective intracellular delivery of an alkaloid drug (galantamine) into PC12 neuronal cells in response to managing Alzheimer's disease (AD). Ligand-functionalized nanoliposomes were produced and validated for their physicochemical properties, in silico molecular mechanics energy relationships, ex vivo cytotoxicity, peptide coupling efficiency (PCE), drug entrapment efficiency (DEE), drug release, fluorometry and confocal microscopy. Particle sizes of the nanoliposomes ranged from 127 nm to 165 nm (PdI=0.39-0.03), zeta potential values of -18 mV to -36 mV, PCE from 40% to 78% while DEE ranged from 42% to 79%. The surface morphology of the nanoliposomes was stable, spherically and uniform in shape. Thermal behavior and Fourier transform infrared (FTIR) analyses confirmed that galantamine and the peptide-ligand were incorporated into the inner core and surface of the nanoliposomes, respectively. The optimized formulation showed sustained drug release (30% of drug released within 48 h). Fluorometry and confocal microscopy revealed that the ligand-functionalized nanoliposomes facilitated galantamine uptake into PC12 neuronal cells via the Serpin Enzyme Complex Receptor in a mediated manner. CytoTox-Glo™ cytotoxicity assay established the low cytotoxicity on PC12 neuronal cells when exposed to native nanoliposomes and the ligand-functionalized nanoliposomes. Response surface analysis demonstrated there was a high degree of correlation between the experimental and fitted values. Furthermore, ex vivo studies showed that the high galantamine accumulation into PC12 neuronal cells was influenced by the post-engineering of peptides on the surface of the galantamine-loaded nanoliposomes. MMER analysis aptly corroborated the experimental findings.
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, 7 York Road, Parktown 2193, Johannesburg, South Africa.
authors.forename: Maluta S
authors.initials: MS
authors.lastname: Mufamadi
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
authors.forename: Sandy
authors.initials: S
authors.lastname: van Vuuren
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Lisa C du
authors.initials: LC
authors.lastname: Toit
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Iyuke
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000818:Animals; D005702:Galantamine / Q000008:administration & dosage* / Q000737:chemistry; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D016716:PC12 Cells; D051381:Rats; D013499:Surface Properties
chemical_list: D008024:Ligands; D008055:Lipids; D008081:Liposomes; D018697:Nootropic Agents; D009842:Oligopeptides; D005702:Galantamine