Sadighian Somayeh, Rostamizadeh Kobra, Hosseini Mir-Jamal, Hamidi Mehrdad, Hosseini-Monfared Hassan
Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Toxicol Lett. 2017 Aug 15;278:18-29. doi: 10.1016/j.toxlet.2017.06.004. Epub 2017 Jun 19.
This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sensitive magnetic nanogels. The NPs showed outstanding entrapment efficiency for doxorubicin (76.6%) with a sustained and high extent of drug release in the acidic media (pH=5-7) compared to the neutral media. Various mitochondrial functional parameters including complex II activity, MDA amount, GSH level, membrane potential collapse, swelling, apoptosis and release of cytochrome c were used to investigate the bio-safety of the nanogels. The findings revealed that the extent of mitochondrial dysfunction of doxorubicin were in the order of free doxorubicin>doxorubicin loaded magnetic nanogels=>doxorubicin loaded Nanogels. The results also revealed that the nanogels and the magnetite nanogels seem to possess promising capability as a safe carrier in comparison of the toxic potential effect of free doxorubicin.
本研究旨在通过分析线粒体功能来评估磁性壳聚糖纳米凝胶作为阿霉素双触发药物载体的生物安全性。在本研究中,采用离子凝胶法制备了含有磁铁矿纳米颗粒(NPs)的壳聚糖/TPP纳米凝胶,作为新型的pH敏感磁性纳米凝胶。与中性介质相比,该纳米颗粒对阿霉素具有出色的包封效率(76.6%),且在酸性介质(pH = 5 - 7)中药物释放持续且程度较高。使用包括复合物II活性、丙二醛含量、谷胱甘肽水平、膜电位崩溃、肿胀、凋亡和细胞色素c释放等各种线粒体功能参数来研究纳米凝胶的生物安全性。研究结果表明,阿霉素导致的线粒体功能障碍程度顺序为:游离阿霉素 > 负载阿霉素的磁性纳米凝胶 > 负载阿霉素的纳米凝胶。结果还表明,与游离阿霉素的潜在毒性作用相比,纳米凝胶和磁铁矿纳米凝胶似乎具有作为安全载体的良好潜力。