Chemical modification of chitosan as a gene carrier in vitro and in vivo

Kim, Tae Hee; Jiang, Hu‐Lin; Jere, Dhananjay; Park, In Kyu; Cho, Myung‐Haing; Nah, Jae‐Woon; Choi, Yun‐Jaie; Akaike, Toshihiro; Cho, Chong‐Su

doi:10.1016/j.progpolymsci.2007.05.001

Cited by 299 publications

(145 citation statements)

References 154 publications

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“…Polyplexes elaborated with high-MW chitosans are very stable and excellent extracellular DNA protectors, but they show, at the same time, low buffer capacity and transfection efficiency (Lu et al, 2009). According to the DDA, high-DDA chitosan vectors have shown better DNA-binding capacity and more efficient transfection than complexes formed with low-DDA chitosan (Kim et al, 2007). For this reason, we have used Novafect O15 and O25 ultrapure oligochitosans (UOCs), which have been previously reported as efficient nonviral vectors for gene delivery in vitro and in vivo (Klausner et al, 2010;Puras et al, 2013a,b).…”

Section: Introductionmentioning

confidence: 99%

Improving transfection efficiency of ultrapure oligochitosan/DNA polyplexes by medium acidification

et al. 2014

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Context: Ultrapure oligochitosans (UOCs) have recently been reported as efficient nonviral vectors for corneal and retinal gene delivery. However, the influence of some physicochemical factors on the transfection efficiency, such as the pH, remains unclear. Deeper in vitro research of these factors could provide valuable information for future clinical applications. Objective: The aim of this study is to determine the influence of the pH decrease on the transfection efficiency of UOC/pDNA polyplexes in HEK293 and ARPE19 cells. Materials and methods: We elaborated self-assembled UOC/pCMS-EGFP polyplexes. The influence of the most important factors on the particle size and the zeta potential was studied by an orthogonal experimental design. We evaluated, in vitro, the cellular uptake and the transfection efficiency by flow cytometry, and the cytotoxicity of the vectors by CCK-8 assay.Results and discussion: The pH of the medium strongly influences the physicochemical properties of the polyplexes, and by its modulation we are able to control their superficial charge. A significant increase on the cellular uptake and transfection efficiency of UOCs was obtained when the pH was acidified. Neither of our UOC/pCMS-EGFP polyplexes caused cytotoxicity; however, cells treated with Lipofectamine 2000ä showed decreased cell viability. Conclusion: This kind of UOC vectors could be useful to transfect cells that are in an acidic environment, such as tumor cells. However, additional in vivo studies may be required in order to obtain an effective and safe medicine for nonviral gene therapy purpose.

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Section: Introductionmentioning

confidence: 99%

Improving transfection efficiency of ultrapure oligochitosan/DNA polyplexes by medium acidification

et al. 2014

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“…Chitosan has been recognised in the past decade as a good candidate for gene delivery due to its properties as low toxicity, biodegradability and versatility as a carrier for intravenous and oral administration [1,2]. Also, the ability to condense efficiently with DNA forming tight polyplexes is important to avoid the degradation by DNAses [3].…”

Section: Introductionmentioning

confidence: 99%

Effect of ionic strength solution on the stability of chitosan–DNA nanoparticles

Picola

Busson

Casé

et al. 2013

Journal of Experimental Nanoscience

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Chitosan-DNA nanoparticles employed in gene therapy protocols consist of a neutralised, stoichiometric core and a shell of the excess of chitosan which stabilises the particles against further coagulation. At low ionic strength, these nanoparticles possess a high stability; however, as the ionic strength increases, it weakens the electrostatic repulsion which can play a decisive part in the formation of highly aggregated particles. In this study, new results about the effect of ionic strength on the colloidal stability of chitosan-DNA nanoparticles were obtained by studying the interaction between chitosans of increasing molecular weights (5, 10, 16, 29, 57 and 150 kDa) and calf thymus DNA. The physicochemical properties of polyplexes were investigated by means of dynamic light scattering, static fluorescence spectroscopy, optic microscopy, transmission electronic microscopy and gel electrophoresis. After subsequent addition of salt to the nanoparticles solution, secondary aggregation increased the size of the polyplexes. The nanoparticles stability decreased drastically at the ionic strengths 150 and 500 mM, which caused the corresponding decrease in the thickness of the stabilising shell. The morphologies of chitosan/DNA nanoparticles at those ionic strengths were a mixture of large spherical aggregates, toroids and rods. The results indicated that to obtain stable chitosan-DNA nanoparticles, besides molecular weight and N/P ratio, it is quite important to control the ionic strength of the solution.

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“…Considering the specific anatomy of the airways, it is traditionally believed that droplets and/or particles with aerodynamic diameter within the range of 1 -3 μm will present appreciable deposition in to chitosan, have rendered increased stability and longer circulation time to chitosan/DNA complexes due to the prevention of aggregation. Hydrophobic derivatives produced by binding N-dodecyl, deoxycholic acid, alkyl groups and stearic acid to the polymer or binding 5-cholanic acid to glycol chitosan, have demonstrated to increase transfection efficiency, while N-dodecylated chitosan also improved the thermal stability of DNA (31).…”

Section: Introductionmentioning

confidence: 99%

“…Urocanic acid-modified chitosan (32), chitosan-graft-polyethyleneimine and polypropyl acrylic acid-modified chitosan have all been described as approaches for pH-sensitive chitosan modification to enhance its transfection efficiency (31). Increased transfection efficiency was also achieved by coupling chitosan to a carboxyl-terminated Nisopropylacrylamide/vinyl laurate, derived from N-isopropylacrylamide which is a well known temperature-sensitive polymer (33).…”

Section: Introductionmentioning

confidence: 99%

The potential of chitosan for pulmonary drug delivery

Grenha

Al‐Qadi

Seijo

et al. 2010

Journal of Drug Delivery Science and Technology

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A Grenha, S Al-Qadi, B Seijo, C Remuñán-López, 2010. AbstractThe administration of drugs through the pulmonary route offers great advantages, but also requires overcoming many challenges. There is a need to develop appropriate carriers for each active molecule to be delivered to the desired site in the lung, either for a local or a systemic effect. The polysaccharide chitosan is a very promising material for this purpose, given its demonstrated properties of biodegradability and biocompatibility, as well as mucoadhesivity and ability to enhance macromolecules permeation. In this review, the potential of chitosan to develop drug carriers for delivery to the lung will be discussed.The most important features that can support its selection will be explained. Besides, different approaches to increase its performance, especially concerning solubility, permeation-enhancing properties and gene transfection efficiency, will be presented.Special emphasis will be placed on information of different chitosan-based carriers, namely nanoparticles and microparticles, intended for pulmonary drug delivery.3

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Chemical modification of chitosan as a gene carrier in vitro and in vivo

Cited by 299 publications

References 154 publications

Improving transfection efficiency of ultrapure oligochitosan/DNA polyplexes by medium acidification

Improving transfection efficiency of ultrapure oligochitosan/DNA polyplexes by medium acidification

Effect of ionic strength solution on the stability of chitosan–DNA nanoparticles

The potential of chitosan for pulmonary drug delivery

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