PEI-alginate nanocomposites: Efficient non-viral vectors for nucleic acids

Patnaik, Satyakam; Arif, Mohammed; Pathak, Atul; Singh, Naresh; Gupta, Kailash C.

doi:10.1016/j.ijpharm.2009.10.041

Cited by 41 publications

(26 citation statements)

References 17 publications

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“…Taken together, all of these results show that NPs and pNPs have excellent stability against varied conditions, including physiological and storage environments. Furthermore, to the best of our knowledge, the stability of pNPs may be superior to that of other gene delivery vectors like PEGylated vectors, 8,10,19,30,32,[34][35][36] which is manifested through their stable size, zeta potential, pDNA-retarding capacity, structure, and the high transfection efficacy after the aforementioned treatments. But because related data were obtained under different experimental conditions and characterization methods, such comparison may be unscientific.…”

Section: Storage Stabilitymentioning

confidence: 98%

“…4,5,7,[11][12][13][14][15][16][17] Additionally, introducing anionic polymer such as anionic polysaccharide is able to improve the polyplex stability and the transfection efficiency by conferring the charge shielding and biodegradability, aiding the rupture of endo-/lysosome and gene release and decreasing cytotoxicity. 5,[18][19][20][21][22] Based on these studies, we engineered a novel brush copolymer of lipopolysaccharide-amine (LPSA) as a cytosolic delivery vector by introducing anionic polysaccharide of oxidized alginate (OA) and Cho to polyethyleneimine (PEI) with molecular weight of 1.8k dalton (PEI 1.8k), where OA and Cho-graft-PEI act as the backbone and side chains, respectively. Encouragingly, LPSA can spontaneously and quickly self-assemble into nanopolymersomes (NPs) in water at a concentration higher than 1.38×10 -3 mg/mL.…”

Section: Introductionmentioning

confidence: 99%

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Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Wang¹,

Chen²,

Wang³

et al. 2015

IJN

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Successful in vivo gene delivery mediated by nonviral vectors requires efficient extracellular and intracellular gene delivery, but few studies have given attention to the former. That is why numerous gene delivery systems have succeeded in vitro, while the expected clinical success has not come about. To realize efficient extracellular gene delivery, the stability of vectors and/or their complexes with genes in body fluids is first required, which prevents loaded genes from premature unloading and degradation. Furthermore, the storage stability of vectors under common conditions is important for their widespread applications. Lipopolysaccharide-amine nanopolymersomes (NPs), a gene vector developed by our group recently, have higher than 95% in vitro transfection efficiency in mesenchymal stem cells when delivering pEGFP , and induce significant angiogenesis in zebrafish when delivering plasmid encoding vascular endothelial growth factor deoxyribonucleic acid ( pVEGF ). To reveal their extracellular delivery ability and storage stability, in this study their stability in various simulant physiological environments and storage conditions was systematically studied by monitoring their changes in disassembly, size, zeta potential, and transfection efficiency. Additionally, damage to the mitochondria of mesenchymal stem cells was evaluated. Results show that NPs and plasmid deoxyribonucleic acid (pDNA)-loaded NPs (pNPs) have acceptable stability against dilution, anions, salts, pH, enzyme, and serum, presumably assuring their efficient extracellular delivery in vivo. Moreover, both the lyophilized NPs at room temperature and NP/pNP solution at 4°C have high storage stability, and pNPs show low damage to the mitochondria. The acceptable stability of NPs combined with compatibility and efficient gene transfection highlight their huge potential in the clinic as a gene delivery vector.

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Section: Storage Stabilitymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Wang¹,

Chen²,

Wang³

et al. 2015

IJN

View full text Add to dashboard Cite

show abstract

“…(Fischer et al, 2003; Intra and Salem, 2008; Nimesh and Chandra, 2009; Swami et al, 2007). PEI can be modified to reduce toxicity and its free amine groups can be used to conjugate cell binding or targeting ligands (Beyerle et al, 2010; Biswal et al, 2010; Bonsted et al, 2008; Breunig et al, 2008; Diebold et al, 1999a; Kang et al, 2010; Kim et al, 2008; Merkel et al, 2009b; Moore et al, 2008; Ogris M, 1999; Patnaik et al, 2010; Petersen et al, 2002; Zintchenko et al, 2008a). …”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

Kim

Jiang

Jacobi

et al. 2012

International Journal of Pharmaceutics

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Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. In this study, we develop and characterize a delivery system for siRNA composed of polyethylenimine (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric stabilization, and mannose serves as a cell binding ligand for macrophages. The PEI-PEG-mannose delivery system was constructed in two different ways. In the first approach, mannose and PEG chains are directly conjugated to the PEI backbone. In the second approach, mannose is conjugated to one end of the PEG chain and the other end of the PEG chain is conjugated to the PEI backbone. The PEI-PEG-mannose delivery systems were synthesized with 3.45 – 13.3 PEG chains and 4.7 – 3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were found to range from 169nm to 357nm. Gel retardation assays showed that the PEI-PEG-mannose polymers are able to efficiently complex with siRNA at low N/P ratios. Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could enter cells and localized in the lysosomes at 2 hours post-incubation. Pegylation of the PEI reduced toxicity without any adverse reduction in knockdown efficiency relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without any significant reduction in knockdown efficiency relative to PEI alone. Conjugating mannose to PEI via the PEG spacer generated superior toxicity and gene knockdown activity relative to conjugating mannose and PEG directly onto the PEI backbone.

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“…7 By modification with alginate (Alg), cytotoxicity of PEI (25 kDa)-Alg (4.8%) NPs is almost negligible. 8 Cytotoxicity of PEI-Alg NPs is lower than PEI NPs in delivering siRNA. 9 Alg is considered to be biocompatible, nontoxic, nonthrombogenic and nonimmunogenic and is approved by the US Food and Drug Administration for various medical applications.…”

Section: Introductionmentioning

confidence: 98%

“…10 As a linear anionic polysaccharide, Alg can reduce PEI toxicity by neutralizing positive charge of PEI and therefore suppress PEI cytotoxicity. 8,9 However, potential cytotoxicity of PEI-Alg NPs is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells

Wang

Tan

Wang

et al. 2017

IJN

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Polyethyleneimine (PEI)–alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI–Alg NPs remains unknown. CD34 + VEGFR-3 + endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies. Cytotoxicity of the NPs was analyzed by reactive oxygen species (ROS) production, lactate dehydrogenase leakage and induction of apoptosis. The level of autophagy was assessed with expression of Beclin-1 and LC3 and formation of autophagic structures and amphisomes. Colocalization of LC3-positive puncta and the NPs was determined by LC3–GFP tracing. Cytotoxicity of PEI NPs was reduced greatly after modification with Alg. PEI–Alg NPs were distributed in mitochondria, rough endoplasmic reticula and nuclei as well as cytoplasm. After phagocytosis of the NPs, expression of Beclin-1 mRNA and LC3 protein was upregulated, and the number of LC3-positive puncta, autophagic structures and amphisomes increased significantly. The number of lysosomes also increased obviously. There were LC3-positive puncta in nuclei, and some puncta were colocalized with the NPs. These results demonstrate that the activated autophagy promotes degradation of PEI–Alg NPs via multiple pathways.

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PEI-alginate nanocomposites: Efficient non-viral vectors for nucleic acids

Cited by 41 publications

References 17 publications

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells

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PEI-alginate nanocomposites: Efficient non-viral vectors for nucleic acids

Cited by 41 publications

References 17 publications

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

Autophagy promotes degradation of polyethyleneimine&ndash;alginate nanoparticles in endothelial progenitor cells

Contact Info

Product

Resources

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Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells