De Smedt S C, Demeester J, Hennink W E
Faculty of Pharmacy, Ghent University, Belgium.
Pharm Res. 2000 Feb;17(2):113-26. doi: 10.1023/a:1007548826495.
Gene transfer to humans requires carriers for the plasmid DNA which can efficiently and safely carry the gene into the nucleus of the desired cells. A series of chemically different cationic polymers are currently being investigated for these purposes. Although many cationic polymers indeed condense DNA spontaneously, which is a requirement for gene transfer in most types of cells, the physicochemical and biopharmaceutical behavior of the current generation of polyplexes severely limits an efficient gene transfer in vitro and especially in vivo. This paper summarizes recent physicochemical and biological information on polyplexes and aims to provide new insights with respect to this type of gene delivery system. Firstly, the chemical structure of frequently studied cationic polymers is represented. Secondly, the parameters influencing condensation of DNA by cationic polymers are described. Thirdly, the surface properties, solubility, aggregration behavior, degradation and dissociation of polyplexes are considered. The review ends by describing the in vitro and in vivo gene transfection behavior of polyplexes.
将基因转移到人体需要用于质粒DNA的载体,该载体能够高效且安全地将基因导入目标细胞的细胞核。目前正在研究一系列化学性质不同的阳离子聚合物用于此目的。尽管许多阳离子聚合物确实能自发地凝聚DNA,这是大多数类型细胞中基因转移的一个必要条件,但当前一代多聚体的物理化学和生物药学行为严重限制了其在体外尤其是体内的高效基因转移。本文总结了关于多聚体的最新物理化学和生物学信息,旨在为这类基因递送系统提供新的见解。首先,展示了经常研究的阳离子聚合物的化学结构。其次,描述了影响阳离子聚合物凝聚DNA的参数。第三,考虑了多聚体的表面性质、溶解性、聚集行为、降解和解离。综述最后描述了多聚体的体外和体内基因转染行为。