Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Poojappura, Thiruvananthapuram, Kerala 695012, India.
Int J Pharm. 2011 May 30;410(1-2):125-37. doi: 10.1016/j.ijpharm.2011.02.067. Epub 2011 Mar 17.
Despite multitude of beneficial features, chitosan has poor water solubility and transfection ability which affect its gene delivery efficacy. The two features are improved when certain chemical modifications are incorporated into the chitosan parent backbone. This strategy is adopted here, by coupling galactose and spermine into the chitosan backbone. The conjugation was determined with FTIR and (1)H NMR and nanoparticle morphology was assessed by TEM and AFM techniques. Particle size, zeta potential, buffering capacity and DNA binding ability gave encouraging result of enhanced solubility and stability. In vitro studies of GCSM in HepG2 cell lines displayed low cytotoxicity and improved transfection. We also identified the preference of receptor mediated internalization for nanoparticles cellular uptake by treating with cellular uptake inhibitors. The results evidently led us to comprehend that galactosylated chitosan-g-spermine could be considered as a promising chitosan derivative for conducting nanoparticle mediated gene delivery.
尽管壳聚糖具有多种有益特性，但它的水溶性和转染能力较差，这影响了其基因传递的效果。当将某些化学修饰引入壳聚糖主链时，可以改善这两个特性。本研究采用这种策略，通过将半乳糖和亚精胺偶联到壳聚糖主链上。通过傅里叶变换红外光谱（FTIR）和（1）H 核磁共振（NMR）确定了偶联，通过透射电子显微镜（TEM）和原子力显微镜（AFM）技术评估了纳米颗粒的形态。粒径、Zeta 电位、缓冲能力和 DNA 结合能力都给出了令人鼓舞的结果，表明其水溶性和稳定性得到了提高。在 HepG2 细胞系中的 GCSM 的体外研究显示出低细胞毒性和转染效率的提高。我们还通过用细胞摄取抑制剂处理来鉴定受体介导的内吞作用对纳米颗粒细胞摄取的偏好。这些结果使我们清楚地认识到，半乳糖化壳聚糖-g-亚精胺可以被认为是一种有前途的壳聚糖衍生物，可用于进行纳米颗粒介导的基因传递。
