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Targeting Etoposide to Acute Myelogenous Leukaemia Cells Using Nanostructured Lipid Carriers Coated With Transferrin Publisher Pubmed



Khajavinia A1 ; Varshosaz J1 ; Dehkordi AJ2
Authors
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Authors Affiliations
  1. 1. Faculty of Pharmacy and Novel Drug Delivery Systems Research Centre, Department of Pharmaceutics Isfahan, University of Medical Sciences, Isfahan, Iran
  2. 2. Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Centre, Department of Biotechnology Isfahan, University of Medical Sciences, Isfahan, Iran

Source: Nanotechnology Published:2012


Abstract

The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide. © 2012 IOP Publishing Ltd Printed in the UK & the USA.
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