Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Liu, Chengchu; Zhu, Qing; Wu, Wenhui; Xu, Xiaolin; Wang, Xiaoyu; Gao, Shen; Liu, Kehai

doi:10.2147/ijn.s36179

Cited by 14 publications

(5 citation statements)

References 31 publications

(24 reference statements)

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“…The majority of cationic polymers have a high buffering capacity, disrupting endosomes during transfection, thereby facilitating the escape of the polymer/DNA complex [ 46 , 58 ]. Figure 5 shows that the CBX-MG-PEI had a relatively high buffering capacity at a pH ranging from 4 to 7, compared with pure water.…”

Section: Resultsmentioning

confidence: 99%

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Modification of Branched Polyethyleneimine Using Mesquite Gum for Its Improved Hemocompatibility

et al. 2021

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In the present study, the modification of branched polyethyleneimine (b-PEI) was carried out using mesquite gum (MG) to improve its hemocompatibility to be used in biomedical applications. In the copolymer synthesis process (carboxymethylated mesquite gum grafted polyethyleneimine copolymer (CBX-MG-PEI), an MG carboxymethylation reaction was initially carried out (carboxymethylated mesquite gum (CBX-MG). Subsequently, the functionalization between CBX-MG and b-PEI was carried out using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as crosslinking agents. The synthesis products were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Thermogravimetric analysis showed that CBX-MG and CBX-MG-PEI presented a lower decomposition temperature than MG. The CBX-MG-PEI has a high buffer capacity in the pH range of 4 to 7, similar to the b-PEI. In addition, the CBX-MG-PEI showed an improvement in hemocompatibility in comparison with the b-PEI. The results showed a non-hemolytic property at doses lower than 0.1 µg/mL (CBX-MG-PEI). These results allow us to propose that this copolymer be used in transfection, polymeric nanoparticles, and biomaterials due to its physicochemical and hemocompatibility properties.

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Section: Resultsmentioning

confidence: 99%

“…After adjusting the initial pH to 10.0 with 0.1 M NaOH, 25 µL increments of 0.1 M HCl were titrated into the solution while measuring the pH response with a pH electrode. The recorded pH varied from 10.0 to 3.0 [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Modification of Branched Polyethyleneimine Using Mesquite Gum for Its Improved Hemocompatibility

et al. 2021

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“…Many works have been published about biodegradable polymeric gene carriers that showed that biodegradability can reduce their cytotoxicity (T. I. Kim et al, 2009; C. Liu et al, 2012; Petersen, Merdan, Kunath, Fischer, & Kissel, 2002; Yu et al, 2009; Zhao, Roesler, & Kissel, 2011).…”

Section: Resultsmentioning

confidence: 99%

Design of PEI-conjugated bio-reducible polymer for efficient gene delivery

Nam

Kim

2018

International Journal of Pharmaceutics

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The poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)) was designed previously as a bio-reducible efficient gene delivery carrier. However, the high weight ratio required to form the polyplexes between poly(CBA-DAH) with pDNA is still a problem that needs to be addressed. To solve this problem and increase the transfection efficiency, poly(ethylenimine) (PEI, 1.8 kDa) was conjugated to poly(CBA-DAH) via disulfide bond. The PEI conjugated poly(CBA-DAH) (PCDP) can bind with pDNA at a very low weight ratio of 0.5 and above, like PEI 25 kDa, and form the polyplexes with nano-size (102-128 nm) and positive surface charge (27-34 mV). PCDP and PCDP polyplexes had negligible cytotoxicity and indicated similar or better cellular uptake than the comparison groups such as PEI 25 kDa and Lipofectamine® polyplexes. To confirm the transfection efficiency, the plasmid DNA (pDNA) encoded with the luciferase reporter gene (gWiz-Luc) and green fluorescent protein reporter gene (GFP) were used and treated with PCDP into the A549, Huh-7, and Mia PaCa-2 cells. PCDP/pDNA polyplexes showed highest transfection efficiency in all tested cell lines. In the luciferase assay, PCDP polyplexes showed 10.2 times higher gene transfection efficiency than Lipofectamine® polyplexes in mimic in vivo conditions (30% FBS, A549 cells). The VEGF siRNA expressing plasmid (pshVEGF), which is constructed as a therapeutic gene by our previous work, was delivered by PCDP into the cancer cells. The VEGF gene expression of PCDP/pshVEGF polyplexes was dramatically lower than control and the VEGF gene silencing efficiencies of PCDP/pshVEGF (w/w; 10/1) polyplexes were 54% (A549 cells), 77% (Huh-7 cells), and 66% (Mia PaCa-2 cells). In addition, PCDP/pshVEGF had reduced cell viability rates of about 31% (A549 cells), 39% (Huh-7 cells), and 42% (Mia PaCa-2 cells) and showed better results than all comparison groups. In the transfection efficiency and VEGF silencing assay, PCDP polyplexes showed better results than poly(CBA-DAH) at 4-fold lower weight ratio. The data of all experiments demonstrate that the synthesized PCDP could be used for efficient gene delivery and could be widely applied.

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“…Visualization is carried out using ethidium bromide or SYBR Green under 300 nm UV light. Agarose gel electrophoresis can be used to study binding affinity of chitosan to nucleic acids during complexation [84], release capacity, protection against endonucleases [73] and stability [84,109].…”

Section: Characterization Techniques Of the Biophysical Propertiesmentioning

confidence: 99%

Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies

2018

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Non-viral gene delivery vectors have lagged far behind viral ones in the current pipeline of clinical trials of gene therapy nanomedicines. Even when non-viral nanovectors pose less safety risks than do viruses, their efficacy is much lower. Since the early studies to deliver pDNA, chitosan has been regarded as a highly attractive biopolymer to deliver nucleic acids intracellularly and induce a transgenic response resulting in either upregulation of protein expression (for pDNA, mRNA) or its downregulation (for siRNA or microRNA). This is explained as the consequence of a multi-step process involving condensation of nucleic acids, protection against degradation, stabilization in physiological conditions, cellular internalization, release from the endolysosome (“proton sponge” effect), unpacking and enabling the trafficking of pDNA to the nucleus or the siRNA to the RNA interference silencing complex (RISC). Given the multiple steps and complexity involved in the gene transfection process, there is a dearth of understanding of the role of chitosan’s structural features (Mw and degree of acetylation, DA%) on each step that dictates the net transfection efficiency and its kinetics. The use of fully characterized chitosan samples along with the utilization of complementary biophysical and biological techniques is key to bridging this gap of knowledge and identifying the optimal chitosans for delivering a specific gene. Other aspects such as cell type and administration route are also at play. At the same time, the role of chitosan structural features on the morphology, size and surface composition of synthetic virus-like particles has barely been addressed. The ongoing revolution brought about by the recent discovery of CRISPR-Cas9 technology will undoubtedly be a game changer in this field in the short term. In the field of rare diseases, gene therapy is perhaps where the greatest potential lies and we anticipate that chitosans will be key players in the translation of research to the clinic.

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Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Cited by 14 publications

References 31 publications

Modification of Branched Polyethyleneimine Using Mesquite Gum for Its Improved Hemocompatibility

Modification of Branched Polyethyleneimine Using Mesquite Gum for Its Improved Hemocompatibility

Design of PEI-conjugated bio-reducible polymer for efficient gene delivery

Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies

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