Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev

School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
Advanced drug delivery reviews (Impact Factor: 15.04). 09/2009; 62(1):12-27. DOI: 10.1016/j.addr.2009.08.004
Source: PubMed


Among non-viral vectors, chitosan and chitosan derivatives have been developed in vitro and in vivo for DNA and siRNA delivery systems because of their cationic charge, biodegradability and biocompatibility, as well as their mucoadhesive and permeability-enhancing properties. However, the transfection efficiency of chitosan is too low for clinical application. Studies indicated that the transfection efficiency depends on a series of chitosan-based formulation parameters, such as the Mw of chitosan, its degree of deacetylation, the charge ratio of chitosan to DNA/siRNA (N/P ratio), the chitosan salt form used, the DNA/siRNA concentration, pH, serum, additives, preparation techniques of chitosan/nucleic acid particles and routes of administration. In this paper, chitosan-based formulations for the delivery of DNA and siRNA were reviewed to facilitate the process of chitosan vector development for clinical application. In addition to formulation optimization, chitosan structure modification or additive incorporation is an effective way to improve the stability of the polyplex in biological fluids, enhance targeted cell delivery and facilitate endo-lysosomal release of the complex. In summary, the transfection efficiency of chitosan-based delivery systems can be adjusted by changing formulation-related parameters.

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    • "Its positive charge promotes electrostatic interactions between the pSiNP and negatively charged oligonucleotides and cell membranes, facilitating both the loading of particles and uptake of the nanocarrier into the cell interior [38]. Chitosan has several interesting features relevant to drug delivery applications [14] [37] [39] [40], including its mucoadhesive properties which enhance mucosal penetration. Previously, Wu and Sailor [41] used chitosan hydrogel to cap porous silicon dioxide films in order to provide a pH-responsive insulin release. "
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    ABSTRACT: Porous silicon nanoparticles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and characterization of thermally hydrocarbonized pSiNPs (THCpSiNPs) and chitosan-coated THCpSiNPs for therapeutic oligonucleotide delivery. Chitosan coating after oligonucleotide loading significantly improves sustained oligonucleotide release and suppresses burst release effects. Moreover, cellular uptake, endocytosis, and cytotoxicity of oligonucleotide-loaded THCpSiNPs have been evaluated in vitro. Standard cell viability assays demonstrate that cells incubated with the NPs at a concentration of 0.1 mg/mL are 95% viable. In addition, chitosan coating significantly enhances the uptake of oligonucleotide-loaded THCpSiNPs across the cell membrane. Moreover, histopathological analysis of liver, kidney, spleen, and skin tissue collected from mice receiving NPs further demonstrates the biocompatible and non-inflammatory properties of the NPs as a gene delivery vehicle for intravenous and subcutaneous administration in vivo. Taken together, these results suggest that THCpSiNPs provide a versatile platform that could be used as efficient vehicles for the intracellular delivery of oligonucleotides for gene therapy.
    Nano Research 04/2015; 8(6). DOI:10.1007/s12274-015-0715-0 · 7.01 Impact Factor
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    • "Considering the favorable properties of chitosan for gene delivery purposes (Mao et al., 2010; Buschmann et al., 2013), its inherent anticancer activity (Tan et al., 2009; Noh et al., 2010; Huang et al., 2012; Liu et al., 2014; Ki et al., 2014), and our previous results that support the use of ultrapure oligochtiosan (UOC) as efficient delivery system for Abbreviations: UOC, ultrapure oligochitosan; EGFP, enhanced green fluorescent protein; AAV, adeno-associated virus; EMEM, Eagles's minimal essential medium; DMEM, Dulbecco's modified Eagle's medium; MW, molecular weight; TEM, transmission electron microscopy. * Corresponding author at: Paseo de la Universidad 7, 01006 Vitoria Gasteiz, Spain. "
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    ABSTRACT: Ultrapure oligochitosans have been recently reported as efficient non-viral vectors for the delivery of pCMS-EGFP plasmid (5.5 Kbp) to the cornea and retina. However, the delivery of oncolytic adenoviral plasmids (40 Kbp) represents a unique challenge. In this work, we elaborated self assembled O15 and O25 UOC/pAdTLRGD polyplexes, and we studied the influence of the N/P ratio, the pH of the transfection medium and the salt concentration on the particle size and zeta potential by an orthogonal experimental design. All polyplexes showed a particle size lower than 200nm and a positive zeta potential. These parameters were influenced by the N/P ratio, salt concentration, and pH of the transfection medium. The selected polyplexes were able to bind, release, and protect the plasmid from DNase degradation. Transfection experiments in HEK293 and A549 cell lines demonstrated that UOC/pAdTLRGD polyplexes were able to deliver the plasmid and transfect both cell lines. These results suggest that O15 and O25 UOC based polyplexes are suitable for future in vivo applications. Copyright © 2014. Published by Elsevier B.V.
    International Journal of Pharmaceutics 12/2014; 479(2). DOI:10.1016/j.ijpharm.2014.12.062 · 3.65 Impact Factor
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    • "We used the method developed by Zhang et al. (2010) to successfully deliver dsRNA and suppress gene expression in mosquito larvae (Anopheles gambiae). This approach utilizes the biopolymer chitosan for encapsulation, protection and delivery of nucleic acids (Mao et al. 2010; Rudzinski & Aminabhavi 2010). We followed the protocol in "
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    ABSTRACT: Reverse genetic tools are essential for characterizing phenotypes of novel genes and testing functional hypotheses generated from next-generation sequencing studies. RNA interference (RNAi) has been a widely used technique for describing or quantifying physiological, developmental, or behavioral roles of target genes by suppressing their expression. The marine intertidal copepod Tigriopus californicus has become an emerging model for evolutionary and physiological studies, but this species is not amenable to most genetic manipulation approaches. Since crustaceans are susceptible to RNAi-mediated gene knockdown, we developed a simple method for delivery of gene-specific double-stranded RNA that results in significant suppression of target gene transcription levels. The protocol was examined on five genes of interest, and for each, at least 50% knockdown in expression was achieved. While knockdown levels did not reach 100% in any trial, a well-controlled experiment with one heat-shock gene showed unambiguously that such partial gene suppression may cause dramatic changes in phenotype. Copepods with suppressed expression of heat-shock protein beta 1 (hspb1) exhibited dramatically decreased tolerance to high temperatures, validating the importance of this gene during thermal stress, as proposed by a previous study. The application of this RNAi protocol in T. californicus will be invaluable for examining the role of genes putatively involved in reproductive isolation, mitochondrial function, and local adaptation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Molecular Ecology Resources 12/2014; 15(4). DOI:10.1111/1755-0998.12359 · 3.71 Impact Factor
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