Singh Rahul Pratap, Sharma Gunjan, Singh Sanjay, Bharti Shreekant, Pandey Bajarangprasad L, Koch Biplob, Muthu Madaswamy S
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Mater Sci Eng C Mater Biol Appl. 2017 Aug 1;77:446-458. doi: 10.1016/j.msec.2017.03.225. Epub 2017 Mar 27.
The aim of this work was to formulate chitosan-folate conjugated multi-walled carbon nanotubes for the lung cancer targeted delivery of docetaxel. The chitosan-folate conjugate was synthesized and the conjugation was confirmed by Fourier transform infrared spectroscopy. The multi-walled carbon nanotubes were characterized for their particle size, polydispersity, zeta potential, surface morphology, drug encapsulation efficiency and in vitro release study. The in vitro cellular uptake, cytotoxicity, and cell cycle analysis of the docetaxel/coumarin-6 loaded multi-walled carbon nanotubes were carried out to compare the effectiveness of the formulations. The biocompatibility and safety of chitosan-folate conjugated multi-walled carbon nanotubes was analyzed by lung histopathology in comparison with marketed docetaxel formulation (Docel™) and acylated multi-walled carbon nanotubes. The cellular internalization study shown that the chitosan-folate conjugated multi-walled carbon nanotubes could be easily internalized into the lung cancer cells through a folate receptor-mediated endocytic pathway. The IC values exhibited that chitosan-folate conjugated multi-walled carbon nanotubes could be 89-fold more effective than Docel™ in human lung cancer cells (A549 cells).
这项工作的目的是制备壳聚糖-叶酸共轭多壁碳纳米管,用于多西他赛的肺癌靶向递送。合成了壳聚糖-叶酸共轭物,并通过傅里叶变换红外光谱确认了共轭。对多壁碳纳米管的粒径、多分散性、zeta电位、表面形态、药物包封效率和体外释放进行了研究。进行了载有多西他赛/香豆素-6的多壁碳纳米管的体外细胞摄取、细胞毒性和细胞周期分析,以比较制剂的有效性。与市售多西他赛制剂(Docel™)和酰化多壁碳纳米管相比,通过肺组织病理学分析了壳聚糖-叶酸共轭多壁碳纳米管的生物相容性和安全性。细胞内化研究表明,壳聚糖-叶酸共轭多壁碳纳米管可通过叶酸受体介导的内吞途径轻松内化到肺癌细胞中。IC值显示,壳聚糖-叶酸共轭多壁碳纳米管在人肺癌细胞(A549细胞)中的有效性可能比Docel™高89倍。