Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA

Richardson, Simon C. W.; H, Kolbe; Duncan, Ruth

doi:10.1016/s0378-5173(98)00378-0

Cited by 502 publications

(204 citation statements)

References 25 publications

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“…This result is in agreement with previously published reports a dose of just 20 μg/mL of PEI was enough to cause cytotoxicity whereas 630 μg/mL of chitosan was required to induce a cytotoxic response [14,57]. OCS has been investigated in a number of studies and has been shown to be even less cytotoxic than PCS [58][59][60].…”

Section: Discussionsupporting

confidence: 82%

Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Raftery

Tierney

Curtin

et al. 2015

Journal of Controlled Release

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Section: Discussionsupporting

confidence: 82%

Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Raftery

Tierney

Curtin

et al. 2015

Journal of Controlled Release

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“…For example, recent evidence shows that low molecular weight preparations of polycations such as chitosan, polyethyleneimine (PEL) and b-cyclodextrincontaining polymers are significantly less toxic than high molecular weight polycations both in cultured cells and in animals. [10][11][12] Additionally, the distance between charge centres along the backbone of a polycation has been shown to affect the toxicity. 12 Thus, the molecular architecture of the nonviral delivery system can modulate the toxicity, and these data suggest that the toxicity should be controllable.…”

Section: Nonviral Vectorsmentioning

confidence: 99%

Intelligent polymers as nonviral vectors

2005

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The successful gene therapy largely depends on the vector type that allows a selective and efficient gene delivery to target cells with minimal toxicity. Nonviral vectors are much safer and cheaper, can be produced easily in large quantities, and have higher genetic material carrying capacity. However, they are generally less efficient in delivering DNA and initiating gene expression as compared to viral vectors, particularly when used in vivo. As nonviral vectors, polycations may work well for efficient cell uptake and endosomal escape, because they do form compact and smaller complexes with plasmid DNA and carry amine groups, which give positive charge and buffering ability that allows safe escape from endosome/lysosome. However, this is a disadvantage in the following step, which is releasing the plasmid DNA within the cytosol. In order to initiate transcription and enhance gene expression, the polymer/plasmid complex should dissociate after releasing from endosome safely and effectively. There are also other limitations with some of the polycationic carriers, for example, aggregation, toxicity, etc. Intelligent polymers, also called as 'stimuli responsive polymers', have a great potential as nonviral vectors to obtain site-, timing-, and duration period-specific gene expression, which is already exhibited in recent studies that are briefly summarized here. Gene Therapy (2005) 12, S139-S145.

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“…Also, the ability to condense efficiently with DNA forming tight polyplexes is important to avoid the degradation by DNAses [3]. The chitosan-DNA interaction is driven mainly by the electrostatic interaction between the amino groups of chitosan and the charged phosphate groups of DNA [4,5] and in a slightly acid medium, this interaction is fully favoured since the most of the amine groups will be charged.…”

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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Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA

Cited by 502 publications

References 25 publications

Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds

Intelligent polymers as nonviral vectors

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

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