Evaluation of Cytotoxicity and Antimicrobial Activity of Experimental Composites Containing Chitosan-Silver Oxide Particles Against Two Main Pathogenic Bacteria in Periodontal Disease.

INTRODUCTION: Bacterial biofilm is known as the main cause of periodontal disease. Generally, the anaerobic Gram-negative, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are considered the most identified bacteria. OBJECTIVE: This study aimed to investigate the antimicrobial effect and cytotoxicity of two experimental composites containing chitosan-silver oxide (CH-Ag2O) particles. MATERIALS AND METHODS: Four experimental groups, including Ag2O and CH, along with two composites of CH-Ag2O 20 and CH-Ag2O 60 mg, were prepared. Antimicrobial activity was performed against Porphyromonas gingivalis (ATCC#33277) and Fusobacterium nucleatum (ATCC#25586) using the agar dilution method. Moreover, the cytotoxicity assay was performed on human gingival fibroblasts (HGF) by the use of the MTT method. The obtained data were analyzed with descriptive methods, one-way ANOVA, and Tukey's LSD tests. RESULTS: The antibacterial activity of both composites was higher than both CH and Ag2O, and the greatest antibacterial properties were presented in CH-Ag2O 60. In all three measurements (24, 48, and 72h), the greatest cytotoxicity was seen in Ag2O, followed by CH, CH-Ag2O 20, and CH-Ag2O 60 in descending order, respectively. The cytotoxicity of these components was related to the concentration and not to the time of exposure. The results showed that Ag2O in 3.7 and 7.5 µg/ml concentrations and CH-containing groups in 250 and 500 µg/ml were toxic to the cultured HGF. CONCLUSION: The experimental composite containing CH-Ag2O 60 showed the greatest antibacterial properties against two periodontal pathogens evaluated. In order to clarify the clinical significance of composite cytotoxicity, further clinical studies are necessary.

Design and characterization of adipose-derived mesenchymal stem cell loaded alginate/pullulan/hyaluronic acid hydrogel scaffold for wound healing applications.

Recently, significant attention has been focused on the progression of skin equivalents to facilitate faster wound healing and thereby skin restoration. The main aim of this study was the design and characterization of a novel polysaccharide-based hydrogel scaffold by using alginate, pullulan, and hyaluronic acid polymers to provide an appropriate microenvironment to deliver Adipose-derived mesenchymal Stem Cells (ASC) in order to promote wound healing in an animal model. Characterization of synthesized hydrogel was done by using a field emission scanning electron microscope (FE-SEM), Fourier Transform-Infrared spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC). Also, contact angle analysis, the swelling and mechanical tests were performed. As a result of in vitro studies, cells can be attached, alive, and migrate through the prepared hydrogel scaffold. Finally, the therapeutic effect of the cell-seeded hydrogels was tested in the full-thickness animal wound model. Based on obtained results, the hydrogel-ASC treatment improved the healing process and accelerated wound closure.

Introducing and assessing the efficacy of a novel method to reduce enamel damage after orthodontic bracket removal using two herbal-based resin colouring agents: An in vitro study.

PURPOSE: The differentiation of resin remnants from enamel is a critical factor to minimize enamel damage after bracket debonding. This study was conducted to produce, and ascertain the efficacy of two colouring agents in minimizing enamel loss, adhesive and bonding remnants, and surface roughness after debonding. METHODS: Two dyes containing annatto (orange colour) and curcumin (yellow colour) were produced. Seventy-two maxillary premolars were divided into three groups. After bracket bonding and debonding, the adhesive remnant was removed with a fine diamond bur. In groups 1 and 2, the orange and yellow dyes were utilized during the removal process, respectively. In group 3 (control) adhesive was removed with no colouring agent. The buccolingual dimension of the teeth was measured at the occlusal, middle, and apical areas, before bonding and after clean-up. The adhesive remnant index (ARI) and bonding remnant index (BRI) scores were recorded and the surface roughness parameters were measured. Data were analysed by ANOVA, Tukey, and Fisher's exact tests (α=0.05). RESULTS: Enamel loss was significantly lower in the groups cleaned by the use of colouring agents than that of the control group (P<0.05). No bonding agent was observed when the dyes were used, whereas 65% of teeth in the control group showed the remaining bonding material (P<0.001). There was no significant difference in ARI scores or surface roughness alterations among the study groups (P>0.05). CONCLUSION: The two dyes produced in this study were effective in enhancing the visibility of residual resin materials and minimizing enamel loss during the clean-up process.

Synthesis and characterization of polyethyleneimine-terminated poly(ß-amino esters) conjugated with pullulan for gene delivery.

Cationic polymers endowed with a flexible system for condensing DNA, are regarded as effective materials for gene delivery. The synthesis of poly(ß-amino esters) (pBAEs) based on 1,4-butanediol diacrylate-ethanolamine monomer (1.2:1 molar ratio) and 1,4-butanediol diacrylate-ethylene diamine (1:2 molar ratio) was carried out and modification with 1800 Da polyethyleneimine (PEI) at different weight ratios (3 and 1) as well as conjugation with pullulan in various weight ratios of (0.0625, 0.125, 0.25, and 1) was performed. Gel-retardation assay demonstrated that the synthesized polymers were able to condense DNA at low carrier/plasmid (C/P) ratios. The polyplexes with ratio 3 of PEI (pß1/PEI3) were restricted in all C/P ratios and the polyplexes of pß1/PEI3/pull0.125 were condensed at C/P ratios higher than 0.5. The particle size at C/P was approximately about 200 nm with a positive surface charge. The presence of the pullulan in the structure of the synthesized pBAEs could be effective in reducing toxicity of the base polymer. Highest metabolic activity was dedicated to C/P2 of pß2/PEI3/pull0.125 with 80.6% viability. Furthermore, the most efficient gene reporter delivery was seen at C/P ratio of 6 in pß2/PEI3/pull0.125 nanoparticles. Therefore, pullulan grafting could enhance the cellular response of cells in terms of cytotoxicity and transfection efficiency.

The effect of sodium hexametaphosphate on sensitivity and whitening effectiveness of an at-home bleaching gel: a randomized, triple-blinded clinical trial.

OBJECTIVE: Bleaching sensitivity (BS) is the most common adverse effect of tooth bleaching treatments. This study evaluated the effect of adding 1% sodium hexametaphosphate (SHMP) on BS and the whitening effectiveness of a bleaching gel. METHOD AND MATERIALS: Two maxillary quadrants from 26 patients were randomly assigned to the experimental and control groups in a split-mouth design. In the control group the at-home bleaching gel containing 3% hydrogen peroxide, and in the experimental quadrant the same gel with 1% SHMP, were applied in individual trays for 6 hours per night for 2 weeks. The patients' sensitivity to cold and touch as well as spontaneous sensitivity were recorded based on a visual analog scale (VAS). Changes in shade guide units (ΔSGU) and ΔE were measured using a spectrophotometer. Data were analyzed using the Kolmogorov-Smirnov, Mann-Whitney U, Wilcoxon signed-rank test, and independent sample t test. RESULTS: Twenty-four patients completed the study. After 2 weeks, the sensitivity to cold and touch was significantly lower in the intervention group compared to the control (P = .015 and P = .039, respectively). The spontaneous sensitivity revealed no significant alteration between these two groups and during the bleaching period in each group (P > .050). Regarding both color measurements, the bleaching effectiveness in both groups was comparable, with no noticeable difference (P > .050). CONCLUSION: The application of 1% SHMP was able to reduce the BS with no detrimental effect on the at-home bleaching effectiveness. (Quintessence Int 2021;52:596-605; doi: 10.3290/j.qi.b1098303).

The effects of sodium hexametaphosphate combined with other remineralizing agents on the staining and microhardness of early enamel caries: An in vitro modified pH-cycling model.

BACKGROUND: This study was conducted to determine the effects of sodium hexametaphosphate (SHMP) combined with other remineralizing agents on the staining and microhardness of early enamel caries. MATERIALS AND METHODS: in This in vitro study The enamel buccal surfaces of 70 bovine incisors were classified into seven study groups (n = 10). Remineralizing agents were employed alone and in combination with SHMP in different groups, including: (1) 8% SHMP, (2) 2% sodium fluoride, (3) 2% sodium fluoride + SHMP, (4) Remin Pro®, (5) Remin Pro®+SHMP, (6) MI Paste Plus, and (7) MI Paste Plus + SHMP. A modified pH-cycling technique was used to reconstruct the dynamics of caries. Colorimetric and microhardness analyses were conducted before demineralization (T1), after caries formation (T2), and after the remineralizing treatment (T3). The data were analyzed by the one-way analysis of variance and the repeated measurement analysis (P > 0.05). RESULTS: After remineralizing cycles, the experimental groups treated with either SHMP alone or in combination with other materials showed less significant changes in the three variables of color (Δa, Δb, and ΔL) and the overall color change (ΔE). The enamel caries treated with Remin Pro® presented the highest color change, while Remin Pro®+ SHMP resulted in the least changes. The mean value of microhardness after remineralization improved significantly in all groups, except in the MI Paste Plus + SHMP group that showed the lowest value. In contrast, the highest microhardness value was recorded for Remin Pro®, being comparable to that of the sound teeth (P > 0.05). CONCLUSION: SHMP, either alone or combined with remineralizing agents, created the least staining. Remineralizing materials alone showed higher surface hardness, while sodium fluoride alone showed higher surface hardness when combined with SHMP.

Linear and Kinked Oligo(phenyleneethynylene)s as Ideal Molecular Calibrants for Förster Resonance Energy Transfer.

We show that oligo(phenyleneethynylene)s (oligoPEs) are ideal spacers for calibrating dye pairs used for Förster resonance energy transfer (FRET). Ensemble FRET measurements on linear and kinked diads with such spacers show the expected distance and orientation dependence of FRET. Measured FRET efficiencies match excellently with those predicted using a harmonic segmented chain model, which was validated by end-to-end distance distributions obtained from pulsed electron paramagnetic resonance measurements on spin-labeled oligoPEs with comparable label distances.

Polyethylenimine-associated cerium oxide nanoparticles: A novel promising gene delivery vector.

AIMS: The development of highly efficient and low toxic non-viral gene delivery vectors is the most challenging issues for successful application of gene therapy. A particular focus has been on understanding structure-activity relationships for transfection activity and toxicity of polyethylenimine (PEI). During the last decade, the use of cerium oxide nanoparticles (CeO2-NPs) in biomedicine has attracted much attention due to their pH-dependent antioxidant activity. CeO2-NPs provide protection normal cells from various forms of reactive oxygen species, but possess innate cytotoxicity and apoptosis to cancer cells. The purpose of this study was to design a new class of gene carriers by low molecular weight PEI (B-PEI 10 kDa) coordination onto CeO2-NPs. MAIN METHODS: B-PEI 10 kDa was conjugated to CeO2-NPs by Epichlorohydrin linker. Transfection efficiency, cytotoxic and apoptotic effects of pDNA-PEI-CeO2 NPs were evaluated on WEHI 164 cancer cells and normal L929 cells lines. KEY FINDINGS: PEI-CeO2 NPs was able to condense the pDNA at carrier/plasmid (C/P) weight ratios of 0.5. The size and zeta potential of pDNA-PEI-CeO2 NPs were 124 ±â€¯7 nm and 22 ±â€¯2 mV, respectively. The transfection efficacy of synthesized pDNA-PEI-CeO2 NPs improved and the cytotoxicity was decreased compared to pDNA-PEI. Moreover, pDNA-PEI-CeO2 NPs induced more apoptosis than unmodified PEI and CeO2-NPs control groups. pDNA-PEI-CeO2 NPs displayed more transfection, cytotoxicity, and apoptosis in WEHI 164 cancer cells than normal L929 cells. SIGNIFICANCE: In conclusion, PEI-CeO2 nanocarriers could act as a potential candidate for gene and drug delivery to cancerous and tumor cells.

BR2 and CyLoP1 enhance in-vivo SN38 delivery using pegylated PAMAM dendrimers.

The usage of 7-Ethyl-10-hydroxy-camptothecin (SN38) as the most biologically active member of camptothecin family is restricted because of its poor solubility in pharmaceutical solvents. Polyamidoamine (PAMAM) dendrimers, can be used as suitable drug delivery carrier for poorly water soluble molecules. In this study, we prepared two cell penetrating peptides (BR2 and CyLoP1) conjugated formulations of PEGylated PAMAM containing SN38. In vitro cytotoxicity and cellular uptake were investigated on murine colon carcinoma (C26) cell line. Then in vivo antitumor efficacy and survival analysis were studied in C26 mice bearing tumor. Blood serum level in different time points and biodistribution in major organs were determined using fluorometry. In vitro evaluations revealed the IC50 range of 154.4-635 nM in two exposure times for all preparations that was much lower compared to SN38 solution. Cellular uptake studies showed a time-dependent manner and higher values for CPP conjugated dendrimers. In vivo results indicated survival improvements of all prepared formulations and significantly better tumor growth inhibition of most CPP-conjugated formulations compared to Irinotecan. Biodistribution studies confirmed higher tumor accumulations for most of formulations comparing to positive control. In conclusion; prepared CPP-targeted dendrimeric formulations of SN38 exhibited efficient characteristics in tumor inhibitory.

Combined effects of polyacrylamide and nanomagnetite amendment on soil and water quality, Khorasan Razavi, Iran.

Nanotechnology is increasingly being used to remediate polluted soil and water. However, few studies are available assessing the potential of nanoparticles to bind surface particles, decrease erosion, and minimize the loading of water pollutants from agricultural surface discharge. To investigate this potential, we treated in situ field plots with two practical surface application levels of anionic polyacrylamide (PAM only) with and without nanomagnetite (PAM-NM), examined soil physical properties, and evaluated the impact of this amendment on contaminant sorption and soil erosion control. Polyacrylamide and PAM-NM treatments resulted in 32.2 and 151.9 fold reductions in Mn2+, 1.8 and 2.7 fold for PO43--P, and 2.3 and 1.6 fold for NH4+-N, respectively, compared to the control. Thus, we found that the combination of PAM and NM, had an important inhibitory effect on NH4+-N and PO43--P transport from soil-pollutants which can contribute substantially to the eutrophication of surface water bodies. Additionally, since the treatment, especially at a high concentration of NM, was effective at reducing Mn2+concentrations in the runoff water, the combination of PAM and NM may be important for mitigating potential risks associated with Mn2+ toxicity. Average sediment contents in the runoff monitored during the rainfall simulation were reduced by 3.6 and 4.2 fold for the low and high concentration PAM-NM treatments when compared to a control. This treatment was only slightly less effective than the PAM-only applications (4.9 and 5.9 fold, respectively). We report similar findings for turbidity of the runoff (2.6-3.3 fold for PAM only and 1.8-2.3 fold for PAM-NM) which was caused by the effects of both PAM and NM on the binding of surface particles corresponding to an increase in aggregate size and stability. Findings from this field-based study show that PAM-modified NM adsorbents can be used to both inhibit erosion and control contaminant transport.

Novel multilayer microcapsules based on soy protein isolate fibrils and high methoxyl pectin: Production, characterization and release modeling.

In this study, novel microcapsules were produced through the layer by layer adsorption of food-grade and plant-based polyelectrolytes, soy protein isolate (SPI) fibrils and high methoxyl pectin (HMP). The physical properties of the fibrils were investigated by TEM and AFM and the properties of the microcapsules such as size, uniformity, zeta potential, morphology, functional groups, modeling and the release kinetics of limonene were examined. The results revealed that SPI-fibrils had a thickness varying from 1 to 10nm and strand like structure. SEM images showed that the microcapsules were spherical and the thickness increased by the number of layers which led to the improvement of shell strength. The FTIR results confirmed that HMP and SPI-fibrils were adsorbed layer by layer as the walls of microcapsules and presence of limonene was stable into microcapsules. By increasing the number of layers of the shell from 2 to 6, the release rate of limonene decreased significantly. The index n in Rigter-Peppas model indicates that the release mechanism of limonene from multilayer microcapsules followed a non-Fick law. This method of microcapsule production is very simple and could be readily industrialized, especially for the manufacture of food products for vegetarians.

Co-Delivery of Epirubicin and siRNA Using Functionalized Mesoporous Silica Nanoparticles Enhances In vitro and In vivo Drug Efficacy.

Development of drug resistance to anticancer drugs is an important challenge for cancer treatment. Recent studies focus on co-delivery of anticancer drugs and siRNA to overcome this challenge. Mesoporous silica nanoparticles (MSNs) are one of the promising nanoparticles that enable the delivery of drugs and siRNA simultaneously. MSNs coated with copolymer capable of co-delivery of drug and siRNA were prepared and characterized. In the present study, MSNs functionalized with polyethylenimine-polyethylene glycol (PEI-PEG) copolymer were prepared. MSNs were characterized using dynamic light scattering (DLS), Transmission Electron Microscopy (TEM) and elemental analysis. Nanoparticles were loaded with epirubicin hydrochloride (EPI) and anti B-cell lymphoma 2 (BCL-2) siRNA. The in vitro cytotoxicity and in vivo efficacy of different formulations were evaluated. Mean size of MSNs ranged from 98 to 247 nm. EPI release from MSNs was pH-dependent. MSNs loaded with EPI and siRNA showed better in vitro cytotoxicity with 1 µg/mL EPI and 50-400 ng/mL siRNA, besides MSNs loaded with 9 mg/kg EPI and 1.2 mg/kg siRNA resulted in improved in vivo effects compared to EPI or MSNs containing EPI or siRNA alone. The results of in vitro and in vivo studies indicated the synergistic effect of EPI and anti BCL-2 siRNA. This formulation could be a promising nanoparticle for codelivery of drug and siRNA in cancer cells.

Surface functionalized mesoporous silica nanoparticles as an effective carrier for epirubicin delivery to cancer cells.

Recent studies with inorganic nanoparticles modified with functional groups have demonstrated improvement in drug delivery into cancer cells. In the present study, we prepared, characterized, and evaluated mesoporous silica nanoparticles (MSNs) as carriers for epirubicin hydrochloride (EPI) in order to improve the antitumor efficacy of this drug. MSNs were prepared and functionalized with phosphonate, polyethylene glycol (PEG) and polyethylenimine-polyethylene glycol (PEI-PEG) groups. Different nanoparticulate formulations were loaded with EPI. The in vitro cytotoxicity and the in vivo antitumor efficacy of MSNs containing EPI were evaluated versus free EPI. The EPI release from nanoparticles was shown to be pH-dependent. The size of MSNs functionalized with polyethyleneimine-polyethylene glycol (MSN-PEI-PEG) was 123.8 ± 4.8 nm. This formulation showed the best antitumor effects at an EPI dose of 9 mg/kg in C-26 colon carcinoma model. The biodistribution results proved that MSN-PEI-PEG-EPI had a higher tumor accumulation compared to free EPI, 3h after drug administration. The results indicated that this formulation could be effective nanocarriers for anti-tumor therapies.

Flexibility of shape-persistent molecular building blocks composed of p-phenylene and ethynylene units.

Ethynylene and p-phenylene are frequently employed constitutional units in constructing the backbone of nanoscopic molecules with specific shape and mechanical or electronic function. How well these properties are defined depends on the flexibility of the backbone, which can be characterized via the end-to-end distance distribution. This distribution is accessible by pulse electron paramagnetic resonance (EPR) distance measurements between spin labels that are attached at the backbone. Four sets of oligomers with different sequences of p-phenylene and ethynylene units and different spin labels were prepared using polar tagging as a tool for simple isolation of the targeted compounds. By variation of backbone length, of the sequence of p-phenylene and ethynylene units, and of the spin labels a consistent coarse-grained model for backbone flexibility of oligo(p-phenyleneethynylene)s and oligo(p-phenylenebutadiynylene)s is obtained. The relation of this harmonic segmented chain model to the worm-like chain model for shape-persistent polymers and to atomistic molecular dynamics simulations is discussed. Oligo(p-phenylenebutadiynylene)s are found to be more flexible than oligo(p-phenyleneethynylene)s, but only slightly so. The end-to-end distance distribution measured in a glassy state of the solvent at a temperature of 50 K is found to depend on the glass transition temperature of the solvent. In the range between 91 and 373 K this dependence is in quantitative agreement with expectations for flexibility due to harmonic bending. For the persistence lengths at 298 K our data predict values of (13.8 +/- 1.5) nm for poly(p-phenyleneethynylene)s and of (11.8 +/- 1.5) nm for poly(p-phenylenebutadiynylene)s.

Polar tagging in the synthesis of monodisperse oligo(p-phenyleneethynylene)s and an update on the synthesis of oligoPPEs.

One important access to monodisperse (functionalized) oligoPPEs is based on the orthogonality of the alkyne protecting groups triisopropylsilyl and hydroxymethyl (HOM) and on the polar tagging with the hydroxymethyl moiety for an easy chromatographic separation of the products. This paper provides an update of this synthetic route. For the deprotection of HOM protected alkynes, γ-MnO2 proved to be better than (highly) activated MnO2. The use of HOM as an alkyne protecting group is accompanied by carbometalation as a side reaction in the alkynyl-aryl coupling. The extent of carbometalation can be distinctly reduced through substitution of HOM for 1-hydroxyethyl. The strategy of polar tagging is extended by embedding ether linkages within the solubilising side chains. With building blocks such as 1,4-diiodo-2,5-bis(6-methoxyhexyl) less steps are needed to assemble oligoPPEs with functional end groups and the isolation of pure compounds becomes simple. For the preparation of 1,4-dialkyl-2,5-diiodobenzene a better procedure is presented together with the finding that 1,4-dialkyl-2,3-diiodobenzene, a constitutional isomer of 1,4-dialkyl-2,5-diiodobenzene, is one of the byproducts.