Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
J Biomed Mater Res B Appl Biomater. 2012 May;100(4):984-92. doi: 10.1002/jbm.b.32661. Epub 2012 Jan 25.
An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by (1)H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree.
对于转染来说,理想的基因载体既要求安全又要求高效。我们研究了水溶性壳聚糖和聚乙烯亚胺作为编码抗血管生成蛋白 TSP-1 的载体在基因传递中的应用。本研究的目的是合成和表征聚乙二醇修饰的阳离子聚合物,以提高抗血管生成基因的转染效率并降低可能的细胞毒性。凝胶电泳研究表明,修饰后的阳离子聚合物具有很强的 DNA 结合能力。此外,(1)H-NMR 也证实了聚乙二醇化聚合物的结构特性。我们研究了 PEG 修饰和涂层颗粒的体外性质,这些颗粒的粒径在 145 到 250nm 之间,具有正的zeta 电位值。此外,壳聚糖基 DNA 复合物对 MCF-7 细胞没有明显的细胞毒性。由于低细胞毒性,与 PEI 相比,我们观察到壳聚糖基制剂具有更高的转染效率。尽管转染研究是在体外条件下进行的,但我们发现 PEG 化后转染效率略有提高。由于其在凝聚和转染 pDNA 方面的效率、低细胞毒性和相对较高的包封率,PEG 修饰的壳聚糖制剂可能是一种很有前途的候选物。