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Transferrin-Targeted Poly(Butylene Adipate)/Terephthalate Nanoparticles for Targeted Delivery of 5-Fluorouracil in Ht29 Colorectal Cancer Cell Line Publisher



Varshosaz J1 ; Riahi S1 ; Ghassami E1 ; Jahaniannajafabadi A2
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy, Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, PO Box 81745-359, Isfahan, Iran
  2. 2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Bioactive and Compatible Polymers Published:2017


Abstract

The purpose of this study was to design 5-fluorouracil-loaded poly(butylene adipate)/terephthalate (Ecoflex®) nanoparticles for targeting colorectal cancer. The nanoparticles were prepared by emulsification-solvent evaporation method and optimized by a full factorial design. The effects of polymer and surfactant concentration, surfactant type, and stirrer rate were studied on the particle size, zeta potential, loading efficiency, and release efficiency of nanoparticles. For production of targeted nanoparticles, chitosan was conjugated to transferrin which was then coated on the surface of Ecoflex nanoparticles via electrostatic interactions. The conjugation of transferrin/chitosan was verified by Fourier transform infrared spectroscopy, ultraviolet spectroscopy, and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) methods and quantified by ultraviolet spectroscopy assay. The cytotoxicity of 5-fluorouracil loaded in targeted and non-targeted nanoparticles was studied on human colon adenocarcinoma cell line (HT29), Michigan Cancer Foundation-7 (MCF-7), and human umbilical vein endothelial cells using MTT (thiazolyl blue tetrazolium bromide) assay. The best results were obtained from nanoparticles prepared by 0.2% of the polymer, 2% of Tween 20, and stirrer speed of 17,500 r/min. The successful conjugation of transferrin/chitosan was confirmed by Fourier transform infrared spectrum and SDS-PAGE results and was about 80%. The targeted nanoparticles showed significantly more cytotoxic effects on HT29 cells compared to free 5-fluorouracil and non-targeted nanoparticles. Blocking transferrin receptors resulted in a significantly higher cell survival for targeted nanoparticles which confirmed receptor-mediated cellular uptake of targeted nanoparticles. © SAGE Publications.
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