PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity

Hashemi, Maryam; Ayatollahi, Sara; Parhiz, Hamideh; Mokhtarzadeh, Ahad; Javidi, Soheila; Ramezani, Mohammad

doi:10.1007/s12010-015-1723-y

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Hashemi et al . 23 reported similar results with a slight decrease in the DNA condensation ability of the G5-DAB dendrimer modified with PEG (MW: 3.4 kDa). Furthermore, G5-PAMAM dendrimer modified with PEG (MW: 3.4 and 5 kDa) showed an increased ability to compact DNA compared to unmodified dendrimers 16 , 24 .…”

Section: Discussionsupporting

confidence: 62%

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Somani

Laskar

Altwaijry

et al. 2018

Sci Rep

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Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07 × 10−3 ± 0.09 × 10−3 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy.

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Section: Discussionsupporting

confidence: 62%

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Somani

Laskar

Altwaijry

et al. 2018

Sci Rep

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“…In our previous study, modified PAMAM dendrimers with PEG and alkylcarboxylate chain had also been used as an appropriate nanoparticle for efficient delivery of GFP reporter gene and Bcl-xL shRNA into cancer cells and mesenchymal stem cells [8,10,38].…”

Section: Discussionmentioning

confidence: 99%

“…Polyamidoamine (PAMAM) dendrimers are considered as one of the most efficient non-viral carriers due to their highly branched, three-dimensional structure, well-defined nanostructures, relatively low toxicity and high loading capacity. They also contain internal cavity for macromolecules encapsulation and free functional groups on their surface for further modifications [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:in vitroandin vivoevaluation

Pishavar

Attaranzadeh

Alibolandi

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is considered as one of the promising approaches for cancer treatment. Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to enhance transfection efficiency through overcoming extracellular and intracellular barriers while reducing PAMAM cytotoxicity. Gene delivery efficiency of synthetized vectors was evaluated by both GFP (green fluorescent protein) reporter gene and TRAIL plasmid in colon cancer cells, in vitro and in vivo. The obtained results demonstrated that PAMAM G4-alkyl-PEG (3%)-Chol (5%)-TRAIL complexes at C/P ratio 4 could significantly increase cell death (29.45%) in comparison with unmodified PAMAM vector (15.5%). Moreover, in vivo study in C26 tumor-bearing BALB/c mice suggested that the prepared non-toxic safe vector could inhibit the tumor growth. This study represented the potent vehicle based on cholesterol-grafted PAMAM dendrimers with alkyl-PEG modification for efficient gene delivery in vitro and in vivo.

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“…3.0G, 4.0G, and 5.0G dendrimers were synthesized using different methods [14][15][16][17]. In the synthesized dendrimeric generations, EDTA constituted the inner core while acrylonitrile made branches of the dendrimers.…”

Section: Synthesis Of Ppi Dendrimers Of Different Generationsmentioning

confidence: 99%

“…A half milliliter of each formulation release medium was withdrawn at predetermined time intervals from 0.5 h to 48 h. After the withdrawal, the release medium was replaced with an equal volume of fresh medium, and the sink conditions were maintained. Then the collected samples were estimated by HPLC and release of donepezil content was determined [17]. All these experiments were performed in triplicate, and the obtained results were presented as the mean±standard deviation.…”

Section: X100mentioning

confidence: 99%

Generation Dependent Targeting Potential of Donepezil Loaded Poly (Propyleneimine) Dendrimer Through Goat Nasal Mucosa

Dwivedi

Kurmi

Kesharwani

et al. 2018

Int J Pharm Pharm Sci

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Objective: In the domain of nano drug delivery, dendrimers are the most explored bioactive polymeric carrier system. The present work was aimed to study the diffusion potential of different generations of Poly (propyleneimine) (PPI) dendrimers on goat nasal mucosa in an ex vivo study and synthesize a stable dendrimer for olfactory drug delivery.Methods: The generations (3.0G, 4.0G, and 5.0G) of PPI dendrimer were synthesized, and PEGylated by MPEG 5000 and then loaded with donepezil. A comparative study was carried out among all generations in term of their drug loading capacity, stability, sustained release behaviour as well as for targeting efficacy. An ex-vivo study was carried out on Franz Diffusion Cell with goat nasal mucosa.Results: The developed G3, G4, and G5 dendrimerformulations had entrapment efficiency of 24.33±0.56%, 40.12±0.62%, and 60.4±0.6%, respectively. The nasal diffusion study revealed that 5.0G PPI dendrimer increased diffusion of donepezil up to 47% as compared to the pure solution of donepezil while 10% improvement in diffusion was seen as compared to 4.0 G PPI dendrimer. Thus obtained results claimed that the drug loading as well as targeting potential of PPI dendrimers increased with the increase in the number of generation. The investigation outcome indicated promising results of 5.0G PPI dendrimer over the 3.0G and 4.0G PPI dendrimer generations for their drug loading capacity, stability, and sustained release action.Conclusion: The 5.0G PPI dendrimer proved its superior candidature over the other lower generations of PPI dendrimers for drug delivery and drug targeting.

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PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity

Cited by 19 publications

References 35 publications

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:in vitroandin vivoevaluation

Generation Dependent Targeting Potential of Donepezil Loaded Poly (Propyleneimine) Dendrimer Through Goat Nasal Mucosa

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