Low molecular weight PEI conjugated pluronic copolymer: Useful additive for enhancing gene transfection efficiency

Abstract

For enhancing the gene delivery efficiency of polyplexes, a new formulation was developed using PEI conjugated Pluronic F127 copolymer as an effective additive. Low molecular weight, branched polyethylenimine Mw 600 (LMW BPEI 600) was conjugated to the terminal end of Pluronic F127. The PEI-modified Pluronic copolymers formed a micellar structure in aqueous solution, similar to that of unmodified Pluronic copolymer. PEI modification of Pluronic copolymer increased the size of micelles while concomitantly raising the critical micelle concentration (CMC). The PEI-modified Pluronic copolymer was used as a micellar additive to enhance the gene transfection efficiency of pre-formulated polyelectrolyte complex nanoparticles composed of luciferase plasmid DNA and branched PEI Mw 25k (BPEI 25k) or polylysine Mw 39k (PLL 39k). The luciferase gene expression levels were significantly enhanced by the addition of the BPEI-modified Pluronic copolymer for the two formulations of BPEI and PLL polyplexes. The results indicated that the BPEI-modified Pluronic copolymer micelles ionically interacted on the surface of DNA/ BPEI (PLL) polyplexes which might facilitate cellular uptake process.

Evaluation of Tris[2-(Acryloyloxy)Ethyl]Isocyanurate Cross-Linked Polyethylenimine as Antisense Morpholino Oligomer Delivery Vehicle in Cell Culture and Dystrophic mdx Mice

“…In contrast, all PEAs at a dose of 20 lg/ml, except C11 [TAEI-PEI 2.0k (1:1), the ratio of the two components used in synthesis], showed cell viability over 80%, which is higher than PEI 25k at 4 lg/ml. This is consistent with earlier reports demonstrating a correlation of lower toxicity to the lower density of positively charged PEI modifications (Nguyen et al, 2000;Cho et al, 2006;Wang et al, 2012a,b). C11 had the highest toxicity among all PEAs, but maintained over 67% cell viability at a dose of 20 lg/ml.…”

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

“…For all cationic polymers, the efficacy of transfection was dependent on the electrostatic interactions and the "proton sponge effect" of PEI. 3 As shown in Figure 10, transfection efficiency of PPs rapidly increased with the increase in ratio of PEI 2KD/Pluronic, which can be explained by the high degree of modification of PEI 2KD leading to an increase in positive surface and structural compactness of the complexes. The highest luciferase expression level was obtained at P105-PEI 2KD, and the Pluronic-g-PEI showed higher gene transfer ability than PEI 2KD.…”

“…1,2 Polycation polyethylenimine (PEI) is one of the most effective and widely studied synthetic nonviral gene delivery vectors, and it has been employed for designing DNA delivery vehicles. 3,4 Through the addition of cationic polymers to DNA, the condensed complexes are spontaneously formed through electrostatic interactions between the positively charged groups of the polycation and the negatively charged phosphate groups of the DNA, resulting in efficient transport of intact DNA into the nucleus. [5][6][7] The whole gene delivery using PEI involves condensation of DNA into compact particles, uptake into cells, release from the endosomal compartment into the cytoplasm, and uptake of the DNA into the nucleus.…”

Vaccination Strategies against Malaria: novel carrier(s) more than a tour de force

“…One of the most effective and widely studied synthetic non-viral gene-delivery vectors is the polycationpolyethylenimine (PEI), which has recently been employed for the design of DNA-delivery vehicles. By adding this cationic polymer to DNA, the condensed complexes can be spontaneously formed through electrostatic interactions, resulting in efficient transport of intact DNA into the nucleus [144][145][146] Gene delivery using PEI involves condensation of DNA into compact particles, uptake into the cells, release from the endosomal compartment into the cytoplasm, and uptake of the DNA into the nucleus. The high transfection efficiency of PEI/DNA complexes should be ascribed to the "proton sponge" effect of PEI [147,148].…”