Biodegradable Polymers for Gene Delivery

Thomas, Thresia; Tajmir-Riahi, H.A.; Pillai, C. K. S.

doi:10.3390/molecules24203744

Cited by 106 publications

(67 citation statements)

References 189 publications

(244 reference statements)

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“…Cationic polymers, such as polyethylenimine, polyamidoamine, chitosan, and dendrimers, are used for gene delivery in vitro and in vivo (Figure 3 ). By condensing DNA into compact particles, they prevent its enzymatic degradation ( 166 ). Upon binding negatively charged DNA molecules, polycationic polymers form polyplexes, which are characterized by the ratio of cationic nitrogen moieties of a polymer (N) to anionic phosphate groups of DNA (P).…”

Section: Methods Of Nucleic Acid Delivery Into Eukaryotic Cellsmentioning

confidence: 99%

Ionic liquids: prospects for nucleic acid handling and delivery

Egorova

Posvyatenko

Larin

et al. 2021

Nucleic Acids Research

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Operations with nucleic acids are among the main means of studying the mechanisms of gene function and developing novel methods of molecular medicine and gene therapy. These endeavours usually imply the necessity of nucleic acid storage and delivery into eukaryotic cells. In spite of diversity of the existing dedicated techniques, all of them have their limitations. Thus, a recent notion of using ionic liquids in manipulations of nucleic acids has been attracting significant attention lately. Due to their unique physicochemical properties, in particular, their micro-structuring impact and tunability, ionic liquids are currently applied as solvents and stabilizing media in chemical synthesis, electrochemistry, biotechnology, and other areas. Here, we review the current knowledge on interactions between nucleic acids and ionic liquids and discuss potential advantages of applying the latter in delivery of the former into eukaryotic cells.

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Section: Methods Of Nucleic Acid Delivery Into Eukaryotic Cellsmentioning

confidence: 99%

Ionic liquids: prospects for nucleic acid handling and delivery

Egorova

Posvyatenko

Larin

et al. 2021

Nucleic Acids Research

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“…8). PEI 25K had a severe cytotoxic effect (Thomas et al, 2019). Several investigations attempted to synthesize PEI derivatives to decrease their cytotoxicity (Han et al, 2018;Lu et al, 2014;Oh et al, 2017).…”

Section: Cytotoxicity Of Pei25k-camentioning

confidence: 99%

Growth inhibition of cholic acid-conjugated polyethylenimine 25K/ p53-EGFP complexes on human carcinoma cells

Weecharangsan¹,

Niyomtham²,

Boon-ek³

et al. 2021

J Appl Pharm Sci

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Cholic acid-conjugated polyethylenimine 25K (PEI 25K-CA) was synthesized and characterized for gene delivery of its buffer capacity, PEI 25K-CA/plasmid DNA complex, zeta potential and particle size, transfection efficiency, cytotoxicity, and carcinoma cell growth inhibition. PEI 25K-CA was complexed with plasmid DNA at the ratio above 0.25/1. PEI 25K-CA/p53-EGFP (p53-enhanced green fluorescent protein) and PEI 25K/p53-EGFP had the particle sizes of 238.2 ± 3.1-529.1 ± 3.6 nm, and the zeta potential of 3.7 ± 1.6-4.3 ± 0.2 mV, respectively. The particle size of the complexes increased with the period of time. PEI 25K-CA/p53-EGFP had transfection efficiency as PEI 25K/ p53-EGFP. The cytotoxicity of PEI 25K-CA was dependent on the concentration of the polymer. The growth inhibition activity was dependent on the dose of p53-EGFP. PEI 25K-CA/pEGFP had better colloidal stability than PEI 25K-CA/ pEGFP. This study concluded that PEI 25K-CA had efficient gene delivery activity as PEI and had lower cytotoxicity and more colloidal stability than PEI 25K.

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“…For the past decades, CS has been largely investigated for various medical and industrial applications [ 33 , 34 , 35 , 36 , 37 ] including drug delivery [ 38 , 39 ]. It is known for its biodegradability [ 40 , 41 ], biocompatibility [ 42 ], and ability to condense DNA [ 4 , 41 , 43 ]. However, the low charge density of CS leads to poor transfection efficiency of CS/DNA systems [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation

Nicolle

Casper

Willimann

et al. 2021

IJMS

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There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; MW 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.

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Biodegradable Polymers for Gene Delivery

Cited by 106 publications

References 189 publications

Ionic liquids: prospects for nucleic acid handling and delivery

Ionic liquids: prospects for nucleic acid handling and delivery

Growth inhibition of cholic acid-conjugated polyethylenimine 25K/ p53-EGFP complexes on human carcinoma cells

Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation

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