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Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti cancer efficacy of the drug     
Yazarlar
Maryam Parisan
Gözde Ünsoy
Pelin Mutlu
Orta Doğu Teknik Üniversitesi, Türkiye
 Serap YALÇIN AZARKAN Serap YALÇIN AZARKAN
Ahi Evran Üniversitesi, Türkiye
Ayşen Tezcaner
Ufuk Gündüz
Orta Doğu Teknik Üniversitesi, Türkiye
Özet
Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine.
CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nano particles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay.
Gemcitabine loading was optimized as 30 mu M by spectrophotometric analyses. Drug release was highest (65%) at pH 4.2, while it was 8% at pH 7.2. This is a desired release characteristic since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4 nm with uniform size distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles.
Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy. (C) 2016 Elsevier B.V. All rights reserved.
Anahtar Kelimeler
Chitosan | Magnetic nanoparticles | Gemcitabine | Targeted drug delivery | Breast cancer
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı EUROPEAN JOURNAL OF PHARMACOLOGY
Dergi ISSN 0014-2999
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 08-2016
Cilt No 784
Sayfalar 121 / 128
Doi Numarası 10.1016/j.ejphar.2016.05.016
Makale Linki http://linkinghub.elsevier.com/retrieve/pii/S0014299916303193