Enamel changes of bleached teeth following application of an experimental combination of chitosan-bioactive glass.

BACKGROUND: Considering the extensive use of bleaching agents and the occurrence of side effects such as enamel demineralization, this study aimed to assess the enamel changes of bleached teeth following the experimental application of chitosan-bioactive glass (CH-BG). METHODS: In this in vitro study, CH-BG (containing 66% BG) was synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Thirty sound human premolars were bleached with 40% hydrogen peroxide, and the weight% of calcium and phosphorus elements of the buccal enamel surface was quantified before and after bleaching by scanning electron microscopy/ energy-dispersive X-ray spectroscopy (SEM, EDX). Depending on the surface treatment of the enamel surface, the specimens were divided into three groups (n = 10): control (no treatment), MI Paste (MI), and CH-BG. Then the specimens were stored in artificial saliva for 14 days. The SEM/EDX analyses were performed again on the enamel surface. Data were analyzed by one-way ANOVA and Tukey's test and a p-value of < 0.05 was considered statistically significant. RESULTS: In all groups, the weight% of calcium and phosphorus elements of enamel decreased after bleaching; this reduction was significant for phosphorus (p < 0.05) and insignificant for calcium (p > 0.05). After 14 days of remineralization, the weight% of both calcium and phosphorus elements was significantly higher compared to their bleached counterparts in both MI and CH-BG groups (p < 0.05). Following the remineralization process, the difference between MI and CH-BG groups was not significant (p > 0.05) but both had a significant difference with the control group in this regard (p < 0.05). CONCLUSIONS: The synthesized CH-BG compound showed an efficacy comparable to that of MI Paste for enamel remineralization of bleached teeth.

Promising clinical outcomes of nano-curcumin treatment as an adjunct therapy in hospitalized COVID-19 patients: A randomized, double-blinded, placebo-controlled trial.

Different immunomodulation strategies have been used to manage COVID-19 due to the complex immune-inflammatory processes involved in the pathogenesis of this infection. Curcumin with its powerful anti-inflammatory and antiviral properties could serve as a possible COVID-19 therapy. In this study, a randomized, double-blinded, placebo-controlled trial was performed to investigate the effectiveness and safety of nano-curcumin oral soft gels as a complementary therapy in moderate-severe COVID-19 patients. Hydroxychloroquine (HCQ) plus sofosbuvir was routinely administered to all 42 COVID-19 patients, who were randomly assigned to receive 140 mg of nano-curcumin or placebo for 14 days. CT scans of the chest were taken, and blood tests were run for all patients at time points of 0, 7, and 14 days. Our results indicated that C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels significantly decreased from baseline in the nano-curcumin-treated group on day 7. Furthermore, blood levels of D-dimer, CRP, serum ferritin, ESR, and inflammatory cytokines including IL-6, IL-8, and IL-10 decreased more significantly in the nano-curcumin-treated group after 14 days. Additionally, the nano-curcumin group showed significant improvements in chest CT scores, oxygen saturation levels, and hospitalization duration. Based on our data, oral administration of nano-curcumin may be regarded as a promising adjunct treatment for COVID-19 patients due to its ability to speed up chest clearance and recovery.

Selective Recognition of Herbicides in Water Using a Fluorescent Molecularly Imprinted Polymer Sensor.

Fluorescent molecularly imprinted polymer (FMIP) optosensor was utilized for the selective identification of 2,4-dichlorophenoxacetic acid (2,4-D) due to worldwide pollution caused by using herbicides in agricultural industry. In this regards, two derivatives of polymerizable 1,8-naphthalimide namely, 1,8-naphthalimide containing thiourea (NI) and diethyl amine tagged 1,8-naphthalimide (NII) were used as the receptors and 2,4-D was applied as a template. Also, precipitation polymerization was applied to prepare the fluorescent molecularly imprinted polymer (FMIP). The morphological, structural and thermal analysis was carried out using SEM, TEM, EDS, BET, FTIR, DSC and TGA for characterizing the fluorescent optosensor. The adsorption efficiency of FMIP and FNIP was studied using Langmuir, Freundlich, BET and Redlich Peterson isotherms. The results represented that the adsorption of 2,4-D on FMIP and FNIP agreed the Freundlich adsorption isotherm with correlation coefficient of 0.9935 and 0.9801, respectively. The prepared sensor was able for the selective determination of 2,4-D salt in the linear range of 5 × 10-7-1 × 10-3 M with a limit of detection of 16.8 nM. The present study revealed that the FMIP prepared by 1,8-naphthalimide derivative (NI) could potentially recognize the trace concentration of 2,4-D. Graphical Abstract Graphical abstract of flourescene switching mechanism in a fluorescent molecularly imprinted polymer sensor.

Silibinin encapsulation in polymersome: A promising anticancer nanoparticle for inducing apoptosis and decreasing the expression level of miR-125b/miR-182 in human breast cancer cells.

Silibinin, a polyphenolic flavonolignan, is well-known as a safe therapeutic drug without any side effects in the treatment of many malignancies especially cancerous cells. In this study, to overcome problems such as low solubility of silibinin and to enhance its delivery to cancerous cells, we encapsulated silibinin in polymersome nanoparticles. Physicochemical measurements such as dynamic light scattering, transmission electron microscopy, scanning electron microscopy, and atomic force microscopy confirmed the proper encapsulation of silibinin in nanoparticles. Furthermore, antiproliferative and apoptotic activities of silibinin encapsulated in polymersome nanoparticles (SPNs) on MDA-MB-231 breast cancer cell line were validated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Annexin V/Propidium Iodide measurement, and cell cycle analysis. In addition, quantitative reverse transcription polymerase chain reaction analysis confirmed that SPNs can repress oncogenic microRNAs (miRNAs) such as miR-125b and miR-182, as well as antiapoptotic genes such as Bcl2. SPNs can also induce overexpression of proapoptotic target genes such as P53, CASP9, and BAX directly and/or indirectly (through regulation of miRNAs). Our results suggested that polymersomes can be used as stable carriers in nano-dimensions and SPNs can be considered as a promising pharmacological agent for cancer therapy.

Curcumin confers protection to irradiated THP-1 cells while its nanoformulation sensitizes these cells via apoptosis induction.

Protection against ionizing radiation (IR) and sensitization of cancer cells to IR are apparently contrasting phenomena. However, curcumin takes on these contrasting roles leading to either protection or enhanced apoptosis in different irradiated cells. Here we studied whether pretreatment with free curcumin or a novel dendrosomal nanoformulation of curcumin (DNC) could exert protective/sensitizing effects on irradiated THP-1 leukemia cells. We employed assays including MTT viability, clonogenic survival, DNA fragmentation, PI/Annexin V flow cytometry, antioxidant system (ROS, TBARS for lipid peroxidation, 8-OHdG and γH2AX for DNA damage, glutathione, CAT and GPx activity, enzymes gene expression), ELISA (NF-κB and Nrf2 binding, TNF-α release), caspase assay, siRNA silencing of caspase-3, and western blotting to illustrate the observed protective role of curcumin in comparison with the opposite sensitizing role of its nanoformulation at a similar 10 µM concentration. The in vivo relevance of this concentration was determined via intraperitoneal administration in mice. Curcumin significantly enhanced the antioxidant defense, while DNC induced apoptosis and reduced viability as well as survival of irradiated THP-1 cells. Nrf2 binding showed an early rise and fall in DNC-treated cells, despite a gradual increase in curcumin-treated cells. We also demonstrated that DNC induced apoptosis in THP-1 cells via caspase-3 activation; whereas in combination with radiation, DNC alternatively employed a caspase-independent apoptosis pathway involving cytochrome c release from mitochondria.

Efficient repairing effect of PEG based tri-block copolymer on mechanically damaged PC12 cells and isolated spinal cord.

Membrane sealing effects of polymersomes made of tri-block copolymer, PEG-co-FA/SC-co-PEG, (PFSP) were studied on isolated spinal cord strips, PC12 cell lines and artificial bilayer following mechanical impact implemented by aneurism clip, sonication and electric shock, respectively. The homogeneity and size of PFSP, membrane permeability and cell viability were assessed by dynamic light scattering, LDH release and MTT assays. According to the results, the biocompatible, physico-chemical, size, surface charge and amphipathic nature of PFSP polymersome makes it an ideal macromolecule to rapidly reseal damaged membranes of cells in injured spinal cord as well as in culture medium. Compound action potentials recorded from intentionally damaged spinal cord strips incubated with PFSP showed restoration of neural excitability by 82.24 % and conduction velocity by 96.72 % after 5 min that monitored in real time. Thus, they triggered efficient instant and sustained sealing of membrane and reactivation of temporarily inactivated axons. Treatment of ultrasonically damaged PC12 cells by PFSP caused efficient cell membrane repair and led to their increased viability. The optimum effects of PFSP on stabilization and impermeabilizing of the lipid bilayer occurred at the same concentrations applied to the damaged cells and spinal cord fibers and was approved by restoration of membrane conductance and calcein release manifested by NanoDrop technique. The unique physico-chemical characteristics of novel polymersomes introduced here, make them capable to reorganize membrane lipid molecules, reseal the breaches and restore the hydrophobic insulation in spinal cord damaged cells. Thus, they might be considered in the clinical treatment of SCI at early stages.

Effect of gamma irradiation on structural and biological properties of a PLGA-PEG-hydroxyapatite composite.

Gamma irradiation is able to affect various structural and biological properties of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties such as molecular weight (GPC), thermal behavior (DSC), wettability (contact angle), cell viability (MTT assay), and alkaline phosphatase activity were studied for the composites and each of their ingredients. The results showed a decrease in molecular weight of copolymer with no change in the glass transition and melting temperatures after gamma irradiation. In general gamma irradiation can increase the activation energy ΔH of the composites and their ingredients. While gamma irradiation had no effect on the wettability of copolymer samples, there was a significant decrease in contact angle of hydroxyapatite and composites with increase in gamma irradiation dose. This study showed an increase in biocompatibility of hydroxyapatite with gamma irradiation with no significant effect on cell viability in copolymer and composite samples. In spite of the fact that no change occurred in alkaline phosphatase activity of composite samples, results indicated a decrease in alkaline phosphatase activity in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG-hydroxyapatite can enhance the composite application as a biomaterial.

Effect of an Experimental Resin-based Sealer (Resil) and AH-26 on Postoperative Pain: A Randomized Controlled Clinical Trial.

Introduction: One of the most common problems in endodontic treatments is post-treatment pain, and sealers might be one of the factors influencing the degree of pain following root canal therapy. The purpose of this study is to compare pain following endodontic treatment using an AH-26 resin sealer against the Resil experimental sealer in mandibular molars with irreversible pulpitis. Materials and Methods: One hundred patients with irreversible pulpitis in the mandibular first or second molar were randomly divided into two groups (n=50) based on the type of sealer applied. Two postgraduate students with at least five years of experience treated all patients. All patients had a single root canal treatment. Postoperative pain scores and analgesic consumption were assessed after 6, 12, 24, and 48 hours and 3, 4, 5, 6, and 7 days after the treatment. The data were statistically analyzed by Fisher's exact or Chi-Square test (to compare the distribution of qualitative variables in two groups), repeated measures ANOVA (to compare changes in pain intensity over time in two groups), Boneferronie (for pairwise comparisons), Friedman, Wilcoxon and Mann-Whitney tests (for assessment of the changes in pain scores over time). The generalized estimating equations (GEE) were used for assessing time and group effects. Results: There was no significant difference in postoperative pain between groups at any of the time points studied (P>0.05), and also for patient analgesic consumption between groups (P>0.05). Both groups recorded the maximum pain levels in the first 6 hours. For each subsequent day postoperatively, the odds ratio (OR) of not using analgesics was 2.078. Conclusion: Resil and AH-26 perform similarly in terms of the occurrence and intensity of postoperative pain in mandibular molar teeth with irreversible pulpitis.

Synthesis of a Calcium Silicate Cement Containing a Calcinated Strontium Silicate Phase.

Objectives: The positive effects of strontium on dental and skeletal remineralization have been confirmed in the literature. This study aimed to assess the properties of a calcium silicate cement (CSC) containing a sintered strontium silicate phase. Materials and Methods: The calcium silicate and strontium silicate phases were synthesized by the sol-gel technique. Strontium silicate powder in 0 (CSC), 10 (CSC/10Sr), 20 (CSC/20Sr), and 30 (CSC/30Sr) weight percentages was mixed with calcium silicate powder. Calcium chloride was used in the liquid phase. X-ray diffraction (XRD) of specimens was conducted before and after hydration. The setting time and compressive strength were assessed at 1 and 7 days after setting. The set discs of the aforementioned groups were immersed in the simulated body fluid (SBF) for 1 and 7 days. The ion release profile was evaluated by inductively coupled plasma-optical emission spectrometry (ICP-OES). Biomineralization on the specimen surface was evaluated by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Data were analyzed by the Kolmogorov-Smirnov test, one-way and mixed ANOVA, Levene's test, and LSD post hoc test (P < 0.05). Results: Except for an increasement in the peak intensity of hydrated specimens, XRD revealed no other difference in the crystalline phases of hydrated and nonhydrated specimens. The compressive strength was not significantly different at 1 and 7 days in any group (P > 0.05). The setting time significantly decreased by an increase in percentage of strontium (P < 0.05). Release of Ca and Si ions significantly decreased by an increase in percentage of strontium (P < 0.05). SEM/EDS showed the formation of calcium phosphate deposits at 1 and 7 days. Conclusion: Incorporation of 10-30 wt% sintered strontium silicate phase as premixed in CSC can significantly decrease the setting time without compromising the compressive strength or biomineralization process of the cement.

Synthesis and characterization of a dental cement based on bioactive glass/zinc oxide modified with organic resin as a novel pulp capping agent.

This study aimed to synthesize and characterize a novel dental pulp capping cement containing bioactive glass (BG)/zinc oxide modified with an organic resin. BG (45S5) with or without ZnO (Zn) and hemaphosphate (HP) combined with a liquid consisting of polyacrylic and itaconic acids (AA) were synthesized and the structural, physical, and mechanical properties were assessed. Hydroxyapatite formation was evaluated by immersion in simulated body fluid. Biological analysis including methyl thiazolyl tetrazolium assay, alizarin red staining, alkaline phosphatase (ALP) activity, and gene expression of odontogenic markers were performed to evaluate the cytotoxic effect and biomineralization potential of the cements on human dental pulp stem cells (hDPSCs). A commercial mineral trioxide aggregate (MTA) served as control. The highest compressive strength value and the shortest setting time were belonged to the BG + HP + AA and BG + AA groups, respectively. The shear bond strength to dentin was the highest for the BG + HP + AA cement. Scanning electron microscope showed only scarce deposits of calcium phosphate formation on the surface of the synthesized cements. BG + HP + AA and BG + HP + Zn + AA groups had significantly lower cytotoxicity than MTA. The mineralization potential of hDPSCs after stimulation by the novel cements increased. Quantitative reverse-transcription-polymerase chain reaction showed higher odontogenic marker expression in hDPSCs exposed to the BG + HP + Zn + AA cement compared to other synthesized cements, although it was higher in MTA group. Based on the obtained results, the novel synthesized cements can be used as appropriate capping agents in the treatment of dental pulp.

Synthesis, Characterization, and Induced Osteogenic Differentiation Effect of Collagen Membranes Functionalized by Polydopamine/Graphene Oxide for Bone Tissue Engineering.

Collagen is one of the most common natural absorbable polymers, which is widely used as a barrier membrane in biomedical fields due to its many desirable biological properties. However, absorbable membranes such as collagen have their own disadvantages such as unpredictable degradation rates, poor rigidity leading to tissue collapse, and limited osteogenic properties and cell adhesion. In this study, a modified collagen membrane with a polydopamine-graphene oxide (PDA/GO) complex was synthesized to improve the characteristics of collagen for bone tissue engineering. The successful synthesis of PDA/GO on collagen membranes was verified using X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The wettability of PDA/GO-modified collagen membranes was considerably improved based on the characterization by water contact angle compared to the uncoated membranes and surface coatings solely by either PDA or GO. The modified PDA/GO coating also enhanced the mechanical properties such as tensile strength and biodegradation rate of collagen membranes. In addition, the PDA/GO coating effectively enhanced the biocompatibility of collagen membranes as verified by the enhanced proliferation and adhesion of human bone marrow stem cells (hBMSCs). Additionally, the effects of PDA/GO coating on the osteogenic differentiation of hBMSCs on collagen membranes were investigated through alkaline phosphatase (ALP) activity and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PDA/GO coating on collagen membranes resulted in a significant increase in osteogenic properties compared with the uncoated collagen membranes. According to the results of the current study, the combination of PDA and GO-modified collagen membranes could be used for bone tissue engineering and biomedical applications.

Evaluation of physical/mechanical properties of an experimental dental composite modified with a zirconium-based metal-organic framework (MOF) as an innovative dental filler.

OBJECTIVES: This study aimed to modify an experimental dental composite using a synthesized nano-structured methacrylated zirconium-based MOF to enhance physical/mechanical properties. METHODS: The previously known Uio-66-NH2 MOF was first synthesized and post-modified with Glycidyl Methacrylate (GMA). Fourier Transform Infrared (FTIR) Spectroscopy and CHNS analysis confirmed the post-modification reaction. The prepared filler was investigated by XRD, BET, SEM-EDS, and TEM. The experimental composite was prepared by mixing 60% wt. of resin matrix with 40% wt. of fillers, including silanized silica (SS) or Uio-66-NH-Me (UM). The experimental composites' depth of cure (DPC) was investigated in five groups (G1 =40% SS, G2 =30%SS+10%UM, G3 =20%SS+20%UM, G4 =10%SS+30%UM, G5 =40%UM). Then flexural strength(FS), Elastic Modulus(EM), solubility(S), water sorption(WS), degree of conversion(DC), polymerization shrinkage(PS), and polymerization stress(PSR) of the groups with DPC of more than 1 mm were investigated. Finally, the cytotoxicity of composites was studied. RESULTS: The groups with more than 20% wt. UM, filler (G4, G5) had lesser than 1 mm DPC. Therefore, we investigated three groups' physical and mechanical properties with lower than 20% UM filler (G1-G3). Within these groups, G3 has a higher FS, EM (P < 0.05), and lower WS and S (P < 0.05). DC dropped in G2 and G3 compared to G1 (p < 0.05), but there was no significant difference between G2 and G3 (P = 0.594). SIGNIFICANCE: This new filler is an innovative coupling-agent free filler and can be part of dental filler technology itself. It can also introduce a new group of dental fillers based on MOFs, but it still needs a complete investigation to be widely used.

Milk thistle nano-micelle formulation promotes cell cycle arrest and apoptosis in hepatocellular carcinoma cells through modulating miR-155-3p /SOCS2 /PHLDA1 signaling axis.

BACKGROUND: Hepatocellular Carcinoma (HCC) is a prevalent form of liver cancer that causes significant mortality in numerous individuals worldwide. This study compared the effects of milk thistle (MT) and nano-milk thistle (N-MT) on the expression of the genes that participate in apoptosis and cell cycle pathways in Huh-7 and HepG2 cells. METHODS: IC50 values of MT and N-MT were determined using the MTT assay. Huh-7 and HepG2 cell lines (containing mutant and wild-type TP53 gene, respectively) were incubated with MT and N-MT for 24h and 48h and the impact of MT and N-MT on the proliferation of these cell lines was evaluated through a comparative analysis. Cell cycle and apoptosis were assessed by flow cytometry after 24h and 48h treatment in the cell lines mentioned. Real-time PCR was used to analyze miR-155-3p, PHLDA1, SOCS2, TP53, P21, BAX, and BCL-2 expression in the cell lines that were being treated. RESULTS: N-MT reduces cancer cell growth in a time and concentration-dependent manner, which is more toxic compared to MT. Huh-7 was observed to have IC50 values of 2.35 and 1.7 µg/ml at 24h and 48h, and HepG2 was observed to have IC50 values of 3.4 and 2.6 µg/ml at 24 and 48h, respectively. N-MT arrested Huh-7 and HepG2 cells in the Sub-G1 phase and induced apoptosis. N-MT led to a marked reduction in the expression of miR-155-3p and BCL-2 after 24h and 48h treatments. Conversely, PHLDA1, SOCS2, BAX, and P21 were upregulated in the treated cells compared to untreated cells, which suggests that milk thistle has the potential to regulate these genes. N-MT reduced the expression of TP53 in Huh-7 cells after mentioned time points, while there was a significant increase in the expression of the TP53 gene in HepG2 cells. No gene expression changes were observed in MT-treated cells after 24h and 48h. CONCLUSION: N-MT can regulate cancer cell death by arresting cell cycle and inducing apoptosis. This occurs through the alteration of apoptotic genes expression. A reduction in the expression of miR-155-3p and increase in the expression of SOCS2 and PHLDA1 after N-MT treatment showed the correlation between miR-155-3p and PHLDA1/SOCS2 found in bioinformatics analysis. While N-MT increased TP53 expression in HepG2, reduced it in Huh-7. The findings indicate that N-MT can function intelligently in cancer cells and can be a helpful complement to cancer treatment.

Design, synthesis, and characterization of a novel dual cross-linked gelatin-based bioadhesive for hard and soft tissues adhesion capability.

Many surgical treatments require a suitable tissue adhesive that maintains its performance in wet conditions and can be applied simultaneously for hard and soft tissues. In the present study, a dual cross-linked tissue adhesive was synthesized by mixing the gelatin methacryloyl (Gel-MA) and gelatin-dopamine conjugate (Gel-Dopa). The setting reaction was based on a photopolymerization process in the presence of a combination of riboflavin and triethanolamine and a chemical cross-linking process attributed to the genipin as a natural cross-linker. Modified gelatin macromolecules were characterized and the best wavelength for free radical generation in the presence of riboflavin was obtained. Tissue adhesives were prepared with 30% hydrogels of Gel-MA and Gel-Dopa with different ratios in distilled water. The gelation occurred in a short time after light irradiation. The chemical, mechanical, physical, and cytotoxicity properties of the tissue adhesives were evaluated. The results showed that despite photopolymerization, chemical crosslinking with genipin played a more critical role in the setting process. Water uptake, degradation behavior, cytotoxicity, and adhesion properties of the adhesives were correlated with the ratio of the components. The SEM images showed a porous structure that could ensure the entry of cells and nutrients into the surgical area. While acceptable properties in most experiments were observed, all features were improved as the Gel-Dopa ratio increased. Also, the obtained hydrogels revealed excellent adhesive properties, particularly with bone even after wet incubation, and it was attributed to the amount of gelatin-dopamine conjugate. From the obtained results, it was concluded that a dual adhesive hydrogel based on gelatin macromolecules could be a good candidate as a tissue adhesive in wet condition.

Synthesis and characterization of a calcium phosphate bone cement with quercetin-containing PEEK/PLGA microparticles.

This study aimed to describe the synthesis and characterization of a calcium phosphate cement (CPC) with polyetheretherketone/poly (lactic-co-glycolic) acid (PEEK/PLGA) micro-particles containing quercetin. CPC powder was synthesized by mixing dicalcium phosphate anhydrate and tetracalcium phosphate. To synthesize PEEK/PLGA microparticles, PLGA85:15 was mixed with 90 wt% PEEK. The weight ratio of quercetin/PLGA/PEEK was 1:9:90 wt%. PEEK/PLGA/quercetin microparticles with 3, 5, and 6 wt% was added to CPC. The setting time, compressive strength, drug release profile, solubility, pH, and porosity of synthesized cement were evaluated. The morphology and physicochemical properties of particles was analyzed by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and inductively coupled plasma. Cytotoxicity was assessed by the methyl thiazolyl tetrazolium assay using dental pulp stem cells. Expression of osteoblastic differentiation genes was evaluated by real-time polymerase chain reaction. Data were analyzed by one-way ANOVA and Tukey's test (alpha = 0.05). The setting time of 3 wt% CPC was significantly longer than 5 and 6 wt% CPC (P< 0.001). The 6 wt% CPC had significantly higher compressive strength than other groups (P= 0.001). The release of quercetin from CPCs increased for 5 d, and then reached a plateau. XRD and FTIR confirmed the presence of hydroxyapatite in cement composition. Significantly higher expression of osteocalcin (OCN) and osteopontin (OPN) was noted in 3 wt% and 6 wt% CPCs. Addition of quercetin-containing PEEK/PLGA microparticles to CPC enhanced its compressive strength, decreased its setting time, enabled controlled drug release, and up-regulated OPN and OCN.

Replacement of hydrochloride in metformin hydrochloride with caprylic acid to investigate its effects on MCF-7 and MDA-MB-231 breast cancer cell lines.

AIMS: Metformin hydrochloride is a highly hydrophilic molecule with low permeability. In the present study, to develop an effective drug to treat the metastatic breast cancer, metformin caprylic acid was synthesized using metformin hydrochloride as a permeable agent. MAIN METHODS: The cytotoxic effects of various concentrations of metformin caprylic acid and metformin hydrochloride (0 to 20 mM) on MCF-7 and MDA-MB-231 breast cancer cells and MCF-10A human mammary epithelial cell line were assessed by the MTT assay. Furthermore, Annexin V, PI staining, and cell flow cytometry assays were performed to evaluate the apoptotic effects. The invasion and migration ability of these cells were evaluated following treatment with equal concentration (3 mM) of the two compounds. KEY FINDINGS: The treatment of tested cell lines with an equal concentration of two chemicals decreased cell viability in a time and dose-dependent manner, where in all cases, metformin caprylic acid caused significantly more apoptosis and invasion inhibition than that of metformin hydrochloride (*p < 0.05). Chemical structures of both compounds were confirmed by FTIR and 1H NMR, 13C NMR. Both chemicals inhibited the migration of MCF-7 and MCF-10A cells, but had no effect on MDA-MB-231 migration. All data are expressed as mean ± SD (n = 3). SIGNIFICANCE: It seems that in an equal concentration, the similarity of the hydrophobic tail of caprylic acid to the cell membrane improves its entrance, while decreasing the drug excretion.

Efficacy of a Novel Bioactive Glass-Polymer Composite for Enamel Remineralization following Erosive Challenge.

Introduction: Dental caries is the most common cause of tooth loss. However, it can be stopped by enhancing remineralization. Fluoride and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) are among the most important remineralizing agents. Recent studies have used bioactive glass as a remineralizing agent in different forms. This study aimed to assess the efficacy of a composite paste (prepared by mixing urethane polypropylene glycol oligomer with bioactive glass powder for easier application). Materials and Methods: Enamel disks were cut out of the buccal surface of extracted sound third molars. The samples were randomly divided into 3 groups of 15 and underwent Vickers microhardness test. X-ray diffraction (XRD) and field emission scanning electron microscopy/energy dispersive X-ray spectroscopy (FESEM/EDS) were performed. All samples were immersed in a demineralizing solution for 14 days. The tests were then repeated. Next, bioactive glass paste, fluoride, and CPP-ACP were applied on the surface of the samples and they were then stored in an artificial saliva for 14 days. The tests were repeated again. The microhardness values were analyzed using repeated measures ANOVA followed by one-way ANOVA and Tukey's post hoc test (P < 0.05). Results: The microhardness of the bioactive glass group was significantly higher than that of other groups (P < 0.05). XRD revealed an enamel structure more similar to sound enamel in the bioactive glass and CPP-ACP groups compared with the fluoride group. FESEM/EDS revealed higher hydroxyapatite deposition in the bioactive glass group than in the other two groups. Conclusions: All three remineralizing agents caused remineralization, but bioactive glass paste had a greater efficacy.

Synthesis and characterization of a photo-cross-linked bioactive polycaprolactone-based osteoconductive biocomposite.

In this study, a light cross-linkable biocomposite scaffold based on a photo-cross-linkable poly (propylene fumarate) (PPF)-co-polycaprolactone (PCL) tri-block copolymer was synthesized and characterized. The developed biodegradable scaffold was further modified with ß-tricalcium phosphate (ß-TCP) bioceramic for bone tissue engineering applications. The developed biocomposite was characterized using H nuclear magnetic resonance and Fourier transform infrared spectroscopy. Moreover, the bioceramic particle size distribution and morphology were evaluated using Brunauer-Emmett-Teller method, X-ray diffraction, and scanning electron microscopy. The mechanical properties and biodegradation of the scaffolds were also evaluated. Cytotoxicity and mineralization assays were performed to analyze the biocompatibility and bioactivity capacity of the developed biocomposite. The characterization data confirmed the development of a biodegradable and photo-cross-linkable PCL-based biocomposite reinforced with ß-TCP bioceramic. In vitro analyses demonstrated the biocompatibility and mineralization potential of the synthesized bioceramic. Altogether, the results of the present study suggest that the photo-cross-linkable PCL-PPF-PCL tri-block copolymer reinforced with ß-TCP is a promising biocomposite for bone tissue engineering applications. According to the results, this newly synthesized material has a proper chemical composition for further clinically-relevant studies in tissue engineering.

Drug release kinetics and biological properties of a novel local drug carrier system.

BACKGROUND: The purpose of this in vitro study was to investigate drug release kinetics and cytotoxicity of a novel drug delivery system for treatment of periodontitis. MATERIALS AND METHODS: This in vitro study addresses the fabrication of a polycaprolactone/alginic acid-based polymeric film loaded with metronidazole, as a basic drug in the treatment of periodontal diseases. Films were prepared by solvent casting technique. Four formulations with different percentages of drug by weight (3%, 5%, 9%, and 13%) were prepared. Drug release kinetics were investigated using ultraviolet-visible spectroscopy during (one week). Data were analyzed using repeated measures ANOVA. Cytotoxicity of drug-loaded system extracts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L929 cells after 24-h incubation. The results were evaluated according to ISO standard 10993-5 and assessed using ANOVA and Tukey's tests at a significance level of P < 0.05. RESULTS: All polymeric films showed a burst drug release followed by a gradual release. Drug release data were fitted well with the first-order kinetic model in all drug-containing formulations indicating that drug release is a fraction of remaining drug in the matrix. Drug release is mainly driven by diffusion of medium into the composite matrix. 3%wt metronidazole-containing formulation exhibited the best MTT result. CONCLUSION: The findings of this study supported the synthesis of drug-loaded periodontal films with 3% metronidazole due to better biological properties along with the ability of acceptable drug release to eradicate anaerobic periodontal bacteria.

Conjugation of Gentamicin to Polyamidoamine Dendrimers Improved Anti-bacterial Properties against Pseudomonas aeruginosa.

Purpose: This study aimed to design gentamicin-conjugated poly (amidoamine) (PAMAM) dendrimers to increase the therapeutic efficiency of gentamicin against Pseudomonas aeruginosa. Methods: Gentamicin-presenting dendrimers were synthesized using MAL-PEG3400-NHS as a redox-sensitive linker to attach gentamicin to the surface of G4 PAMAM dendrimers. The gentamicin molecules were thiolated by using Traut reagent. Then, the functionalized gentamicin molecules were attached to PEGylated PAMAM dendrimers through simple and high selectively maleimide (MAL)-thiol reaction. The structure of gentamicin-conjugated PAMAM dendrimers was characterized and confirmed using nuclear magnetic resonance (NMR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM) imaging. The antibacterial properties of the synthesized complex were examined on P. aeruginosa and compared to gentamycin alone. Results: NMR, DLS, zeta potential analysis, and TEM imaging revealed the successful conjugation of gentamicin to PAMAM dendrimers. Data showed the appropriate physicochemical properties of the synthesized nanoparticles. We found a 3-fold increase in the antibacterial properties of gentamicin conjugated to the surface of PAMAM dendrimers compared to non-conjugated gentamicin. Based on data, the anti-biofilm effects of PAMAM-Gentamicin dendrimers increased at least 13 times more than the gentamicin in normal conditions. Conclusion: Data confirmed that PAMAM dendrimer harboring gentamicin could be touted as a novel smart drug delivery system in infectious conditions.