siRNA Delivery with Chitosan: Influence of Chitosan Molecular Weight, Degree of Deacetylation, and Amine to Phosphate Ratio on in Vitro Silencing Efficiency, Hemocompatibility, Biodistribution, and in Vivo Efficacy

Alameh, Mohamad-Gabriel; Lavertu, Marc; Tran-Khanh, Nicolas; Chang, Ching-Chun; Lesage, Frédéric; Bail, Martine; Darras, Vincent; Chevrier, Anik; Buschmann, Michael D.

doi:10.1021/acs.biomac.7b01297

Cited by 94 publications

(87 citation statements)

References 71 publications

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“…S1a). The importance of Mw on siRNA-chitosan nanoparticle properties is well documented in the literature and its impact on cytotoxicity [17], intracellular release and transfection efficiency has been reported [32,33]. Hence, besides keeping the degree of substitution at 15%, the reaction conditions were mild, and the molar masses of the derivatives (DEAE-CH 130 , DEAE-CH 230 and DEAE-CH 220 ), remained close to those of the deacetylated chitosans (CH and CHH, Table 1).…”

Section: Synthesis and Characterization Of The Deae 15 -Ch Derivativesmentioning

confidence: 97%

Diethylaminoethyl- chitosan as an efficient carrier for siRNA delivery: Improving the condensation process and the nanoparticles properties

Souza

Picola

Shi

et al. 2018

International Journal of Biological Macromolecules

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Chitosan has been indicated as a promising carrier for the preparation of small interfering RNA (siRNA) delivery systems due to its remarkable properties. However, its weak interactions with siRNA molecules makes the condensation of siRNA molecules into nanoparticles difficult. In this work, a non-viral gene delivery system based on diethylaminoethyl chitosan (DEAE-CH) derivatives of varied Mw (25-230 kDa) having a low degree of substitution of 15% was investigated. The presence of secondary and tertiary amino groups strengthened the interaction of siRNA and DEAE-CH derivatives of higher Mw (130 kDa to 230 kDa) and provided the preparation of spherical nanoparticles at low charge ratios (N/P 2 to 3) with low polydispersities (0.15 to 0.2) in physiological ionic strength. Nanoparticles prepared with all derivatives exhibited remarkable silencing efficiencies (80% to 90%) on different cell lines (HeLa, MG-63, OV-3) by adjusting the charge ratios. A selected PEG-folic acid labeled derivative (FA-PEG-DEAE15-CH) was synthesized and its nanoparticles completely inhibited the mRNA expression level of TNF-α in RAW 264.7 macrophages. The study demonstrates that the insertion of DEAE groups provides improved physical properties to chitosan-siRNA nanoparticles and holds potential for in vivo applications.

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Section: Synthesis and Characterization Of The Deae 15 -Ch Derivativesmentioning

confidence: 97%

Diethylaminoethyl- chitosan as an efficient carrier for siRNA delivery: Improving the condensation process and the nanoparticles properties

Souza

Picola

Shi

et al. 2018

International Journal of Biological Macromolecules

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“…Based on published data accumulated over the past decade, average gene silencing efficiencies of 64.6 ± 24.7% in vitro and 61.5 ± 19.6% in vivo have been achieved (Figure and Table ). The three most frequently employed types of polymer nanoparticles for siRNA delivery have been solid polymeric nanoparticles, dendrimers, and hydrogels, but across the wide range of structural designs in polymeric delivery systems, there are a number of proven components that are regularly used: poly(lactic‐co‐glycolic acid) (PLGA), poly‐L‐lysine (PLL), chitosan, and polyethyleneimine (PEI) …”

Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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“…The water solubility of chitosan is low due to the presence of highly crystalline intermolecular and intramolecular hydrogen bonds, and can be greatly influenced by the pH, molecular weight and deacetylation degree [6,9,29]. The solubility of chitosan has been improved by introducing a hydrophilic group on amino or hydroxyl groups.…”

Section: Chitosan Solubilitymentioning

confidence: 99%

Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology

Rashidpour

Pablos

et al. 2020

Polymers

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Chitosan is increasingly used for safe nucleic acid delivery in gene therapy studies, due to well-known properties such as bioadhesion, low toxicity, biodegradability and biocompatibility. Furthermore, chitosan derivatization can be easily performed to improve the solubility and stability of chitosan–nucleic acid polyplexes, and enhance efficient target cell drug delivery, cell uptake, intracellular endosomal escape, unpacking and nuclear import of expression plasmids. As in other fields, chitosan is a promising drug delivery vector with great potential for the fish farming industry. This review highlights state-of-the-art assays using chitosan-based methodologies for delivering nucleic acids into cells, and focuses attention on recent advances in chitosan-mediated gene delivery for fish biotechnology applications. The efficiency of chitosan for gene therapy studies in fish biotechnology is discussed in fields such as fish vaccination against bacterial and viral infection, control of gonadal development and gene overexpression and silencing for overcoming metabolic limitations, such as dependence on protein-rich diets and the low glucose tolerance of farmed fish. Finally, challenges and perspectives on the future developments of chitosan-based gene delivery in fish are also discussed.

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siRNA Delivery with Chitosan: Influence of Chitosan Molecular Weight, Degree of Deacetylation, and Amine to Phosphate Ratio on in Vitro Silencing Efficiency, Hemocompatibility, Biodistribution, and in Vivo Efficacy

Cited by 94 publications

References 71 publications

Diethylaminoethyl- chitosan as an efficient carrier for siRNA delivery: Improving the condensation process and the nanoparticles properties

Diethylaminoethyl- chitosan as an efficient carrier for siRNA delivery: Improving the condensation process and the nanoparticles properties

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology

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