Advanced Pharmaceutical Bulletin (Sep 2016)

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

  • Farhad Jahanfar,
  • Akbar Hasani,
  • Dariush Shanebandi,
  • Mohammad Rahmati,
  • Hamed Hamishehkar

DOI
https://doi.org/10.15171/apb.2016.048
Journal volume & issue
Vol. 6, no. 3
pp. 367 – 375

Abstract

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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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