title: Enhancedin VitroAnti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles.
abstract: Purpose:In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell linesMethods:5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene.Results:The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn't show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug.Conclusion:The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine.
authors.affiliation: Biotechnology Research Center and Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Jahanfar
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Hasani
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanebandi
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rahmati
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
keywords: 5-azacytidine; Cancer; Cytotoxicity; SLN; Solid lipid nanoparticles