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 polyetherPluronic ® 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 hydrophiliclipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus. Conclusion: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.

Preparation and characterization of cationic Pluronic for surface modification and functionalization of polymeric drug delivery nanoparticles

“…Direct experimental data support the conclusion that the membrane affinity of Pluronic derivatives (i.e. Pluronic-polyamine) was improved when compared to that of Pluronic [27,47]. Based on these data we may assume that this feature will be present when Pluronic-amines are on the surface of PLGA NPs.…”

Chemical stabilization of dispersed Escherichia coli for enhanced recovery with a handheld electroflotation system and detection by Loop-mediated Isothermal AMPlification

“…Additionally, pluronic is an amphiphilic molecule that can self-assemble into microstructure micelles [ 38 ]. Surfactant micelles can encapsulate other molecules and have been used widely for the solubilization of drugs and drug delivery [ 39 ]. It is conceivable that pluronic micelles formed around detectable cell material ( i .…”

PEGylated Polyethylenimine Derivative-Mediated Local Delivery of the shSmad3 Inhibits Intimal Thickening after Vascular Injury

“…The limitation of the current study is that PEG-Et 1:1 still exhibited cytotoxicity when the concentration was over 50 μ g/mL, some modifiers such as Pluronic [47], MoS2 [48], and PLLA [49] can be applied for efficient gene delivery, and in order to reduce its cytotoxicity, we can modify the structure of the cationic polymer with other modifiers. In vivo study, we evaluated the results 14 days after vascular injury, we did not select other time points for further evaluations (3 months or one year).…”