Yazarlar |
Maryam Parisan
|
Gözde Ünsoy
|
Pelin Mutlu
Orta Doğu Teknik Üniversitesi, Türkiye |
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 |