title: Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin.
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 IC(50) value of 15-fold lower than free etoposide.
authors.affiliation: Faculty of Pharmacy and Novel Drug Delivery Systems Research Centre, Department of Pharmaceutics Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Khajavinia
authors.forename: Jaleh
authors.initials: J
authors.lastname: Varshosaz
authors.forename: Abbas Jafarian
authors.initials: AJ
authors.lastname: Dehkordi
mesh_terms: D000588:Amines / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D005047:Etoposide / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry; D058726:Nanoconjugates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013096:Spermine / Q000494:pharmacology; D014168:Transferrin / Q000737:chemistry*
chemical_list: D000588:Amines; D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D058726:Nanoconjugates; D014168:Transferrin; D013096:Spermine; D005047:Etoposide; C009317:stearylamine; C003935:dodecylamine