title: Effects of lipid composition and preparation conditions on physical-chemical properties, technological parameters and in vitro biological activity of gemcitabine-loaded liposomes.
abstract: The effects of lipid composition and preparation conditions on the physicochemical and technological properties of gemcitabine-loaded liposomes, as well as the in vitro anti-tumoral activity of various liposome formulations were investigated. Three liposome formulations were investigated: DPPC/Chol/Oleic acid (8:3:1 molar ratio, liposomes A), DPPC/Chol/DPPS (6:3:1 molar ratio, liposomes B) and DPPC/Chol/DSPE-MPEG (6:3:1 molar ratio, liposomes C). Multilamellar liposomes were prepared by using the TLE, FAT and DRV methods, while small unilamellar liposomes were obtained by extrusion through polycarbonate filters. Light scattering techniques were used to characterize liposome formulations. Loading capacity and release profiles of gemcitabine from various liposome formulations were also investigated. Caco-2 cells were used to evaluate in vitro the antitumoral activity of gemcitabine-loaded liposomes with respect to the free drug and also the intracellular drug uptake. Preparation methods and liposome lipid composition influenced both physicochemical parameters and drug delivery features. Liposomes with a size ranging from 200 nm to 7 microm were obtained. The gemcitabine entrapment was higher than that expected probably due to an interaction with the liposome lipid components. The following decreasing loading capacity order was observed: liposome B>liposome C>liposome A. Gemcitabine release from various liposome formulations is modulated by two different processes, i.e. desorption from and permeation through liposomal bilayers. MTT assay showed a greater cytotoxic effect of gemcitabine-loaded liposomes with respect to the free drug. The following decreasing anticancer activity order was observed between the various liposome formulations: liposome C>liposome A>liposome B. The increased anticancer activity is correlated to the ability of the colloidal carrier to increase the intracellular drug uptake. Due to the encouraging results and to the high liposome modularity various applications of potential therapeutic relevance can be envisaged for liposomes.
authors.affiliation: Department of Pharmacobiological Sciences, University Magna Graecia of Catanzaro, Campus Universitario - Building of BioSciences, Viale Europa, I-88100 Germaneto (CZ), Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calvagno
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.forename: Donato
authors.initials: D
authors.lastname: Cosco
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Iannone
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Doldo
authors.forename: Massimo
authors.initials: M
authors.lastname: Frest
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D003102:Colloids / Q000737:chemistry; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D055672:Static Electricity; D013678:Technology, Pharmaceutical / Q000379:methods; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003102:Colloids; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011355:Prodrugs; D003841:Deoxycytidine; C038089:1,2-distearoylphosphatidylethanolamine; D019301:Oleic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002784:Cholesterol; D000093542:Gemcitabine