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N ‐acetylcysteine–PLGA nano‐conjugate: effects on cellular toxicity and uptake of gadopentate dimeglumine
Authors:Elham Poonaki  Mohammad Esfandyar  Hadi Hejazinia  Seyed Esmaeil Sadat Ebrahimi  Morteza Pirali Hamedani  Jafar Farzaneh  Mehdi Shafiee Ardestani
Affiliation:1. Department of Biotechnology, I.A.U., Damghan Iran ; 2. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran Iran ; 3. Department of Medicinal Chemistry, Tehran University of Medical Sciences, Tehran Iran
Abstract:Gadolinium as a contrast agent in MRI technique combined with DTPA causes contrast induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF) which can reduce by usage of antioxidants such as N‐acetyl cysteine by increasing the membrane''s permeability leads to lower cytotoxicity. In this study, N ‐acetyl cysteine‐PLGA Nano‐conjugate was synthesized according to stoichiometric rules of molar ratios andafter assessment by FTIR, NMR spectroscopy and Atomic Force Microscopy (AFM) imaging was combined with Magnevist® (gadopentetate dimeglumine) and its effects on the renal cells were evaluated. MTT 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide] and cellular uptake assays have indicated relatively significant toxicity of magnevist (P  < 0.05) on three cell lines including HEK293, MCF7 and L929 compared to other synthesized ligands that shown no toxicity. Moreover, systemic evaluation has shown no notable changes of blood urea nitrogen (BUN) and creatinine in kidney of mice. In consequence, antioxidant effect was increased as well as the renal toxicity of the contrast agent reduced at the cell level. As a result, PLGA‐NAC nano‐conjugate can be a promising choice for decreasing the magnevist toxicity for treatment and prevention of CIN and will be able to open a new horizon to research on reduction of toxicity of contrast agents by using nanoparticles.Inspec keywords: blood, toxicology, nanofabrication, cellular biophysics, biomedical materials, nanoparticles, chromatography, cancer, biodegradable materials, biomedical MRI, kidney, pH, nanomedicine, patient treatment, diseases, atomic force microscopy, Fourier transform infrared spectraOther keywords: cellular toxicity, gadopentate dimeglumine, contrast agent, magnetic resonance imaging technique, diethylenetriamine pentaacetate, contrast‐induced nephropathy, nephrogenic systemic fibrosis, stoichiometric rules, molar ratios, dimethyl sulphoxide solution, chromatography techniques, nuclear magnetic resonance spectroscopy, atomic force microscopy imaging, Magnevist®, gadopentetate dimeglumine, renal cells, MTT cytotoxicity, human embryonic kidney‐293, L929 cell lines, in vitro conditions, cellular uptake assays, Magnevist uptake, antioxidant effect, renal toxicity, cell level, PLGA nanocarrier, acetylcysteine nanoconjugate, Magnevist toxicity, N‐acetylcysteine–PLGA nano‐conjugate, N‐acetyl cysteine‐poly‐lactic‐co‐glycolic acid nanoconjugate
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