N-[4-(N,N,N-trimethylammonium)benzyl]chitosan chloride: Synthesis, interaction with DNA and evaluation of transfection efficiency

Raik, Sergei V.; Poshina, Daria N.; Lyalina, Tatiana A.; Polyakov, Dmitry; Vasilyev, V. B.; Kritchenkov, Andreii S.; Skorik, Yury А.

doi:10.1016/j.carbpol.2017.11.093

Cited by 35 publications

(12 citation statements)

References 26 publications

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“…Chitosan is an excellent carrier material [7,8,9] because of its good histocompatibility, diversity of biological activities, and absorption of degradation products (glucosamine) in vivo [10]. Chemical modification of chitosan can further improve its functionality [11,12,13,14] (mucosal adhesion, antimicrobial activity, and blood compatibility), such as alkylation, carboxymethylation, or quaternization.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

Sun

Ying

et al. 2019

Pharmaceutics

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Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by ionic crosslinking. Owing to ion interaction, the negatively charged, non-toxic tripolyphosphate (TPP) interacted with the positively charged amino group on the aminated chitosan (AmCS) surface, producing FA-AmCS-TPP nanoparticles, which were then characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), and thermogravimetric analysis (TGA). Their small particle size (175.2 ± 0.99 nm) and good surface positive potential (+42.4 mV) are beneficial for carrying antitumor drugs. We subsequently investigated whether coating of Cur by AmCS allows slow drug release by FA-AmCS-TPP nanoparticles in different pH environments, and estimated the Cur loading efficiency (EE-Cur). Our results showed that the cumulative release rate of Cur at 48 h was 56.2%, and that the EE-Cur reached 94.26 ± 0.91% with nanoparticles composed of 0.10 g AmCS, 10.0 mg FA, 10.0 mg TPP, and 15.0 mg Cur. Additionally, cytotoxicity experiments showed that the Cur/FA-AmCS-TPP nanoparticles had good targeting ability for tumor cells. Therefore, the non-toxic targeted composite nanoparticles had potential as a new antitumor agent that can overcome the limitations of Cur.

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Section: Introductionmentioning

confidence: 99%

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

Sun

Ying

et al. 2019

Pharmaceutics

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“…CS from crab shells (Bioprogress, Schelkovo, Russia) had the following characteristics: a viscosity average molecular weight of 3.7 × 10 4 and a degree of acetylation (DA) of 0.26 [19]. We prepared 4-formyl-n,n,n-trimethylanilinium iodide (FTMA) as previously described [19]. The 4-(n,n-dimethylamino)benzaldehyde, pyridoxal hydrochloride, sodium borohydride, and methyl iodide were purchased from Sigma Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies [19] established that the transfection efficiency is higher with TMAB-CS with a relatively low DS of 0.25 than with highly substituted TMAB-CS due to better polyplex dissociation within the cell. All three CS derivatives were obtained by a two-step one-pot procedure (Figure 1).…”

Section: Synthesis and Nmr Characterization Of Cationic Chitosan Derimentioning

confidence: 96%

“…The obtained derivatives demonstrated good solubility in water and low toxicity; however, their transfection efficiencies were significantly lower than that of the commercially available Lipofectin transfection agent. Nonetheless, further work has confirmed the possibility of controlling the DS by changing the reagent ratios, reaction time, and pH [19].…”

Section: Introductionmentioning

confidence: 97%

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Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency

et al. 2020

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Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH4. This reaction yielded three novel derivatives, n-[4-(n’,n’,n’-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n’,n’,n’’-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by 1H NMR spectroscopy as DS1 = 0.22 for TMAB-CS, DS2 = 0.28 for Pyr-CS, and DS1 = 0.21, DS2 = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110–165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%–70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy.

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“…Chitosan is a popular choice for gene transfer studies because of its low cost, excellent biocompatibility, and notable biodegradability. Moreover, the abundance of primary amines and hydroxyl groups in the chitosan backbone favors tunable chemical modification of the polymer to enhance its efficacy for gene delivery [11,12].…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of Diethylaminoethyl-Chitosan and Methylglycol-Chitosan as Potential Non-Viral Vectors for Gene Therapy

et al. 2018

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Abstract:In this paper, we compared the transfection efficiency and cytotoxicity of methylglycolchitosan (MG-CS) and diethylaminoethyl-chitosan (DEAE-CS I and DEAE-CS II with degrees of substitution of 1.2 and 0.57, respectively) to that of Lipofectamine (used as a reference transfection vector). MG-CS contains quaternary amines to improve DNA binding, whereas the DEAE-CS exhibits pH buffering capability that would ostensibly enhance transfection efficiency by promoting endosomal escape. Gel retardation assays showed that both DEAE-CS and MG-CS bound to DNA at a polysaccharide:DNA mass ratio of 2:1. In Calu-3 cells, the DNA transfection activity was significantly better with MG-CS than with DEAE-CS, and the efficiency improved with increasing polysaccharide:DNA ratios. By contrast, the efficiency of DEAE-CS I and DEAE-CS II was independent of the polysaccharide:DNA ratio. Conversely, in the transfection-recalcitrant JAWSII cells, both Lipofectamine and MG-CS showed significantly lower DNA transfection activity than in Calu-3 cells, whereas the efficiency of DEAE-CS I and DEAE-CS II was similar in both cell lines. The toxicity of DEAE-CS increased with increasing concentrations of the polymer and its degree of substitution, whereas MG-CS demonstrated negligible cytotoxicity, even at the highest concentration studied. Overall, MG-CS proved to be a more efficient and less toxic transfection agent when compared to DEAE-CS.

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N-[4-(N,N,N-trimethylammonium)benzyl]chitosan chloride: Synthesis, interaction with DNA and evaluation of transfection efficiency

Cited by 35 publications

References 26 publications

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency

Comparative Study of Diethylaminoethyl-Chitosan and Methylglycol-Chitosan as Potential Non-Viral Vectors for Gene Therapy

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