Chitosan nanoparticles’ functionality as redox active drugs through cytotoxicity, radical scavenging and cellular behaviour

Sarangapani, Sreelatha; Patil, Ajeetkumar; Ngeow, Yoke Keng; Mohan, Rosmin Elsa; Asundi, Anand; Lang, Matthew J.

doi:10.1039/c8ib00038g

Cited by 31 publications

(28 citation statements)

References 33 publications

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“…nPLGA and nCS are considered as safe drug carriers. [24][25][26][27] This study also confirmed that CS or PLGA had no obvious cytotoxicity on periodontal membrane cells and no impact on their proliferation and may be applied for periodontal bone tissue regeneration. The safe concentration of nAg was found as 40-50 µg.…”

Section: Discussionsupporting

confidence: 72%

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

Xue¹,

Hong

Gao³

et al. 2019

IJN

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ObjectiveThis study aims to produce nanoparticles of chitosan (CS), poly(lactic-co-glycolic acid) (PLGA), and silver and investigate the optimal composite ratio of these three materials for periodontal tissue regeneration.MethodsPLGA nanoparticles (nPLGA), CS nanoparticles (nCS), and silver nanoparticles (nAg) were prepared. The antibacterial properties of single nanoparticles and their effects on the proliferation and mineralization of periodontal membrane cells were investigated. Different ratios of nPLGA and nCS were combined, the proliferation and mineralization of periodontal membrane cells were investigated, and based on the results, the optimal ratio was determined. Finally, nPLGA and nCS in optimal ratio were combined with nAg, and the effects of the complex of these three materials on the proliferation and mineralization of periodontal membrane cells were investigated and tested in animals.ResultsThe single nanoparticles were found to have no cytotoxicity and were able to promote cell mineralization. nCS and nAg in low concentrations showed antibacterial activity; however, nAg inhibited cell proliferation. The nPLGA and nCS complex in 3:7 ratio contributed to cell mineralization and had no cytotoxicity. nPLGA/nCS/nAg complex, which had the optimal proportion of the three materials, showed no cytotoxicity and contributed to cell mineralization.ConclusionnPLGA/nCS/nAg complex had no cytotoxicity and contributed to cell mineralization. The 3:7 ratio of nPLGA/nCS and 50 µg/mL nAg were found as the optimal proportion of the three materials.

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Section: Discussionsupporting

confidence: 72%

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

Xue¹,

Hong

Gao³

et al. 2019

IJN

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“…One study suggested that Chit NPs had an inhibitory activity (Bor et al, 2016), two studies reported no Chit NPs effect (Omar Zaki et al, 2015;Arora et al, 2016) and three reported a stimulating effect (Hu et al, 2011;Sarangapani et al, 2018;Wang et al, 2018) on basal ROS cellular production. Concerning the polymer, same conflicting results were also found (Arora et al, 2016;Salehi et al, 2017;Sarangapani et al, 2018). From our case study, we concluded that, despite no significant differences were found in the cytotoxic profile of both NPs in RAW 264.7 cells, in ROS assay these NPs had different effects when tested at non-cytotoxic concentrations.…”

Section: Discussionmentioning

confidence: 99%

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

Jesus

Marques

Duarte

et al. 2020

Front. Bioeng. Biotechnol.

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Nanoparticles (NPs) assumed an important role in the area of drug delivery. Despite the number of studies including NPs are growing over the last years, their side effects on the immune system are often ignored or omitted. One of the most studied polymers in the nano based drug delivery system field is chitosan (Chit). In the scientific literature, although the physicochemical properties [molecular weight (MW) or deacetylation degree (DDA)] of the chitosan, endotoxin contamination and appropriate testing controls are rarely reported, they can strongly influence immunotoxicity results. The present work aimed to study the immunotoxicity of NPs produced with different DDA and MW Chit polymers and to benchmark it against the polymer itself. Chit NPs were prepared based on the ionic gelation of Chit with sodium tripolyphosphate (TPP). This method allowed the production of two different NPs: Chit 80% NPs (80% DDA) and Chit 93% NPs (93% DDA). In general, we found greater reduction in cell viability induced by Chit NPs than the respective Chit polymers when tested in vitro using human peripheral blood monocytes (PBMCs) or RAW 264.7 cell line. In addition, Chit 80% NPs were more cytotoxic for PBMCs, increased reactive oxygen species (ROS) production (above 156 µg/mL) in the RAW 264.7 cell line and interfered with the intrinsic pathway of coagulation (at 1 mg/mL) when compared to Chit 93% NPs. On the other hand, only Chit 93% NPs induced platelet aggregation (at 2 mg/mL). Although Chit NPs and Chit polymers did not stimulate the nitric oxide (NO) production in RAW 264.7 cells, they induced a decrease in lipopolysaccharide (LPS)-induced NO production at all tested concentrations. None of Chit NPs and polymers caused hemolysis, nor induced PBMCs to secrete TNF-α and IL-6 cytokines. From the obtained results we concluded that the DDA of the Chit polymer and the size of Chit NPs influence the in vitro immunotoxicity results. As the NPs are more cytotoxic than the corresponding polymers, one should be careful in the extrapolation of trends from the polymer to the NPs, and in the comparisons among delivery systems prepared with different DDA chitosans.

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“…Thus an 80% DDA in CH nanoparticles and polymer were able to induce ROS in a concentration-dependent manner, while a 93% DDA did not. Moreover, Sarangapani et al 81 found that with a particular size of positively charged CH nanoparticles, the oxidative stress mechanism can be triggered through ROS generation and the depletion of glutathione, becoming selectively cytotoxic for leukemia cells. Similarly, Martinez et al 60 proposed CH gold nanoparticles (CH-AuNPs) to induce ROS production as a possible treatment for cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Evidence Supporting the Safety of Pegylated Diethylaminoethyl-Chitosan Polymer as a Nanovector for Gene Therapy Applications</p>

Rondon¹,

Benabdoun²,

Vallières³

et al. 2020

IJN

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Purpose: Diethylaminoethyl-chitosan (DEAE-CH) is a derivative with excellent potential as a delivery vector for gene therapy applications. The aim of this study is to evaluate its toxicological profile for potential future clinical applications. Methods: An endotoxin-free chitosan (CH) modified with DEAE, folic acid (FA) and polyethylene glycol (PEG) was used to complex small interfering RNA (siRNA) and form nanoparticles (DEAE 12-CH-PEG-FA 2 /siRNA). Based on the guidelines from the International Organization for Standardization (ISO), the American Society for Testing and Materials (ASTM), and the Nanotechnology Characterization Laboratory (NCL), we evaluated the effects of the interaction between these nanoparticles and blood components. In vitro screening assays such as hemolysis, hemagglutination, complement activation, platelet aggregation, coagulation times, cytokine production, and reactive species, such as nitric oxide (NO) and reactive oxygen species (ROS), were performed on erythrocytes, plasma, platelets, peripheral blood mononuclear cells (PBMC) and Raw 264.7 macrophages. Moreover, MTS and LDH assays on Raw 264.7 macrophages, PBMC and MG-63 cells were performed. Results: Our results show that a targeted theoretical plasma concentration (TPC) of DEAE 12-CH-PEG-FA 2 /siRNA nanoparticles falls within the guidelines' thresholds: <1% hemolysis, 2.9% platelet aggregation, no complement activation, and no effect on coagulation times. ROS and NO production levels were comparable to controls. Cytokine secretion (TNF-α, IL-6, IL-4, and IL-10) was not affected by nanoparticles except for IL-1β and IL-8. Nanoparticles showed a slight agglutination. Cell viability was >70% for TPC in all cell types, although LDH levels were statistically significant in Raw 264.7 macrophages and PBMC after 24 and 48 h of incubation. Conclusion: These DEAE 12-CH-PEG-FA 2 /siRNA nanoparticles fulfill the existing ISO, ASTM and NCL guidelines' threshold criteria, and their low toxicity and blood biocompatibility warrant further investigation for potential clinical applications.

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Chitosan nanoparticles’ functionality as redox active drugs through cytotoxicity, radical scavenging and cellular behaviour

Cited by 31 publications

References 33 publications

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

<p>Evidence Supporting the Safety of Pegylated Diethylaminoethyl-Chitosan Polymer as a Nanovector for Gene Therapy Applications</p>

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