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Docetaxel-Loaded Nanostructured Lipid Carriers Functionalized With Trastuzumab (Herceptin) for Her2-Positive Breast Cancer Cells Publisher Pubmed



Varshosaz J1 ; Davoudi MA2 ; Rasoulamini S3
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medical Nanotechnology, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Source: Journal of Liposome Research Published:2018


Abstract

The aim of the present study was to prepare Herceptin targeted nanostructured lipid carriers (NLCs) of docetaxel (DTX). Herceptin was conjugated by chemical and physical methods to NLCs prepared by solvent extraction technique followed by probe sonication. Different types of fatty amines were used in construction of NLCs. The NLCs were characterized for their antibody coupling efficiency, particle size, zeta potential, polydispersity index, drug entrapment efficiency and drug release profiles. The toxicity of NLCs on MDA-MB-468 (HER2 negative receptor) and BT-474 (HER2 positive) breast cancer cell lines was evaluated by MTT assay. Also their cellular uptake was studied by flow-cytometry and fluorescent microscopy. The results showed the NLCs containing stearyl amine had the lowest particle size, the highest zeta potential and antibody coupling efficiency values. Herceptin binding to NLCs led to reduction in zeta potential and drug entrapment efficiency while, particle size increased. The NLCs containing spermine(SP) released DTX slower than other fatty amines. Non-conjugated nanoparticles containing DTX had more toxicity than the free DTX on both cell lines. Herceptin targeted NLCs caused more mortality on BT-474 cells than MDA-MB-468 cells. Flow-cytometry studies revealed enhanced cellular uptake of nanoparticles chemically conjugated by Herceptin on the BT-474 cells. DTX loaded in chemically conjugated NLCs to Herceptin showed more cytotoxic effects than the physically coated nanoparticles. The Herceptin conjugated NLCs seem promising in oriented delivery of DTX to HER2 positive breast cancer cells. © 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group.
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