title: Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution.
abstract: BACKGROUND
  Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.
  
  
  METHODS
  This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic(®) consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.
  
  
  RESULTS
  Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.
  
  
  CONCLUSIONS
  This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: Baoyue
authors.initials: B
authors.lastname: Ding
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Yin
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.forename: Xueying
authors.initials: X
authors.lastname: Ding
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
mesh_terms: D000704:Analysis of Variance; D002470:Cell Survival / Q000187:drug effects; D003851:Deoxyribonucleases / Q000737:chemistry; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D010316:Particle Size; D010957:Plasmids / Q000493:pharmacokinetics; D020442:Poloxamer / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D020442:Poloxamer; D011094:Polyethyleneimine; D003851:Deoxyribonucleases