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ISSN: 2228-5881      eISSN: 2251-7308  
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Article History
Submitted: 12 Feb 2016
Revised: 25 Apr 2016
Accepted: 27 Apr 2016
First published online: 25 Sep 2016

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Adv Pharm Bull. 2016;6(3):367-375 doi: 10.15171/apb.2016.048

Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

Research Article

Farhad Jahanfar 1,2, Akbar Hasani 2, Dariush Shanebandi 3, Mohammad Rahmati 2, Hamed Hamishehkar 4 *

1 Biotechnology Research Center and Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.



Abstract

Purpose:In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitroeffect of encapsulated 5-azacytidine studied on MCF-7 cell lines

Methods: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 vitroeffect 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 ofRARß2 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.







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Articles by Jahanfar F
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Articles by Rahmati M
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