title: Gemcitabine and tamoxifen-loaded liposomes as multidrug carriers for the treatment of breast cancer diseases.
abstract: The effects of a lipid composition on the physico-chemical and technological properties of a multidrug carrier (MDC) containing both gemcitabine (GEM) and tamoxifen (TMX), as well as its in vitro antitumoral activity on different breast cancer cell lines, were investigated. In particular, the following three different liposomal formulations were prepared: DPPC/Chol/DSPE-mPEG2000 (6:3:1 molar ratio, formulation A), DPPC/Chol/DOTAP (6:3:1 molar ratio, formulation B) and DPPC/Chol/DPPG (6:3:1 molar ratio, formulation C). The colloidal systems were obtained by the TLE technique and the extrusion process allowed us to obtain vesicles having mean sizes of 150-200 nm, while the surface charges varied between 50 mV and -30 mV. Formulation A showed the best encapsulation efficiency between the two compounds and the presence of TMX influenced the release profile of GEM (hydrophilic compound) as a consequence of its effect on the fluidity of the bilayer. An MDC of formulation A was used to effectuate the in vitro cytotoxicity experiments (MTT-test) on MCF-7 and T47D cells. The liposomal MDC provided the best results with respect to the single drug tested in the free form or entrapped in the same liposomal formulation. The CLSM experiments showed a great degree of cell interaction of liposomal MDC after just 6h.
authors.affiliation: Department of Health Sciences, University Magna Græcia of Catanzaro, Campus Universitario S. Venuta - Building of BioSciences, Viale Europa, I-88100 Germaneto (CZ), Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cosco
authors.forename: D
authors.initials: D
authors.lastname: Paolino
authors.forename: F
authors.initials: F
authors.lastname: Cilurzo
authors.forename: F
authors.initials: F
authors.lastname: Casale
authors.forename: M
authors.initials: M
authors.lastname: Fresta
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D003102:Colloids; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005260:Female; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D012995:Solubility; D013629:Tamoxifen / Q000494:pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods; D000093542:Gemcitabine
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000964:Antimetabolites, Antineoplastic; D003102:Colloids; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D000644:Quaternary Ammonium Compounds; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D003841:Deoxycytidine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D002784:Cholesterol; C002773:dimyristoylphosphatidylglycerol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D000093542:Gemcitabine