Long-Term Stability of Chitosan-Based Polyplexes

Romøren, Kristine; Aaberge, Astrid; Smistad, Gro; Thu, Beate; Evensen, Øystein

doi:10.1007/s11095-004-7687-1

Cited by 12 publications

(3 citation statements)

References 27 publications

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“…In recent years, it has been well-established that chitosan/DNA particles provide good stability ( − ). Nevertheless, in vivo results are still rare and rather moderate ( , ), In particular, for challenging routes of application like the oral route, the stability still may be not adequate.…”

Section: Discussionmentioning

confidence: 99%

Role of Sulfhydryl Groups in Transfection? A Case Study with Chitosan−NAC Nanoparticles

2007

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This study investigated the use of chitosan-N-acetylcysteine (NAC) as a non-viral gene carrier. In particular, we aimed to elucidate whether the advantage of thiolation was more pronounced in the stabilization of particles or in the effect of nonspecific sulfhydryl reduction of the target cells. Low-viscosity chitosan was modified by covalent binding of NAC. The resulting conjugate displayed 1.35 mM SH/g polymer. Particles produced via self-assembly of chitosan conjugate and pDNA had a mean particle size of 113.7 nm and a positive zeta-potential. Sulfhydryl group content on the particle surface was investigated by Ellman's test and papain reactivation assay, with the result of about 100 nM SH groups/mL nanoparticle suspension. An oxidation step was performed to stabilize polyplexes via disulfide bonds. The enhanced stability of oxidized particles against both polyanion heparin and alkaline pH was proven by a gel retardation assay. The stabilization was demonstrated to be reversible by treatment with glutathione. Further, the effect of immobilized SH groups and of supplementation with free NAC on transfection efficacy on Caco-2 cells was investigated. The expression of the transgene was raised 2.5-fold and 10-fold with nonoxidized thiomer polyplexes in comparison to polyplexes of unmodified chitosan and oxidized chitosan-NAC, respectively. The impact of sulfhydryl reduction on transfection was assessed via thiol group inactivation with 5,5'-dithiobis-(2-nitrobenzoic acid) (DNTB). This inactivation resulted in a decrease of transfection efficacy. In conclusion, chitosan-NAC conjugate was demonstrated to be beneficial for transfection, either for stabilization via disulfide bonds or for raising the expression of transgene via shifting the redox potential of the target cells.

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Section: Discussionmentioning

confidence: 99%

Role of Sulfhydryl Groups in Transfection? A Case Study with Chitosan−NAC Nanoparticles

2007

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“…It is also a critical factor that helps to predict permeability across biological membranes. The change in particle size and zeta potential of particles can alter the transfection efficiency (39).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle

et al. 2018

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VA-coated lipoplexes exhibited an average particle sizes less than 200 nm and zeta potential around +25 mV both determined using ZetaPALS. Inclusion of VA to liposomal surfaces significantly enhanced their cellular uptake without affecting cytotoxicity. VA-coupled liposomes carrying BMP4-siRNA resulted in a significant reduction in BMP4 and α-SMA at both mRNA and protein levels. Conclusion: VA-coated liposomes were successfully designed to deliver BMP4-siRNA to specifically target HSC. The novel delivery system discussed herein may serve as a potential therapeutic strategy for the treatment of liver fibrosis in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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“…In this study, we develop a novel miRNA functionalized microporous coating technique on Ti implant by lyophilizing miRNA lipoplexes onto the MAO Ti surface. On the basis of prior findings, we hypothesize that this system will possess multiple advantages including long-term stability, , enhanced substrate-mediated transfection possibly from the microporous MAO topography, − and the direct miRNA delivery to the adjacent bone tissues without arousing systemic side effects. The miR-29b and the antimiR-138 that are reported to promote osteogenic differentiation are chosen for functionalization of the Ti surface to obtain enhanced osteogenic activity.…”

Section: Introductionmentioning

confidence: 96%

MicroRNA Functionalized Microporous Titanium Oxide Surface by Lyophilization with Enhanced Osteogenic Activity

Wu¹,

Song²,

Zhao³

et al. 2013

ACS Appl. Mater. Interfaces

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Developing biomedical titanium (Ti) implants with high osteogenic ability and consequent rigid osseointegration is a constant requirement from the clinic. In this study, we fabricate novel miRNA functionalized microporous Ti implants by lyophilizing miRNA lipoplexes onto a microporous titanium oxide surface formed by microarc oxidation (MAO). The microporous titanium oxide surface provides a larger surface area for miRNA loading and enables spatial retention of the miRNAs within the pores until cellular delivery. The loading of lipoplexes into the micropores on the MAO Ti surface is facilitated by the superhydrophilicity and Ti-OH groups gathering of the MAO surface after UV irradiation followed by lyophilization. A high miRNA transfection efficiency was observed in mesenchymal stem cells (MSCs) seeded onto the miRNA functionalized surface with no apparent cytotoxicity. When functionalizing the Ti surface with miR-29b that enhances osteogenic activity and antimiR-138 that inhibits miR-138 inhibition of endogenous osteogenesis, clear stimulation of MSC osteogenic differentiation was observed, in terms of up-regulating osteogenic expression and enhancing alkaline phosphatase production, collagen secretion and ECM mineralization. The novel miRNA functionalized Ti implants with enhanced osteogenic activity promisingly lead to more rapid and robust osseointegration of a clinical bone implant interface. Our study implies that lyophilization may constitute a versatile method for miRNA loading to other biomaterials with the aim of controlling cellular function.

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Long-Term Stability of Chitosan-Based Polyplexes

Abstract: The biological and physicochemical stability of the chitosan-based polyplexes are maintained for 1 year of storage in acetate-buffer at 4 degrees C. The changes in the polyplex characteristics at elevated temperatures may be explained by degradation of both plasmid and chitosan.

Cited by 12 publications

References 27 publications

Role of Sulfhydryl Groups in Transfection? A Case Study with Chitosan−NAC Nanoparticles

Role of Sulfhydryl Groups in Transfection? A Case Study with Chitosan−NAC Nanoparticles

Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle

MicroRNA Functionalized Microporous Titanium Oxide Surface by Lyophilization with Enhanced Osteogenic Activity

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