Synergistic effect of curcumin and tamoxifen loaded in pH-responsive gemini surfactant nanoparticles on breast cancer cells.

BACKGROUND: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. METHODS: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. RESULTS: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. CONCLUSION: The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.

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.

Discovery of a Novel Dual Targeting Peptide for Human Glioma: From In Silico Simulation to Acting as Targeting Ligand.

Purpose: Receptor-mediated transcytosis (RMT) is a more specific, highly efficient, and reliable approach to crossing the blood-brain-barrier (BBB) and releasing the therapeutic cargos into the brain parenchyma. Methods: Here, we introduced and characterized a human/mouse-specific novel leptin-derived peptide using in silico, in vitro and in vivo experiments. Results: Based on the bioinformatics analysis and molecular dynamics (MD) simulation, a 14 amino acid peptide sequence (LDP 14) was introduced and its interaction with leptin-receptor (ObR) was analyzed in comparison with an well known leptin-derived peptide, Lep 30. MD simulation data revealed a significant stable interaction between ligand binding domains (LBD) of ObR with LDP 14. Analyses demonstrated suitable cellular uptake of LDP 14 alone and its derivatives (LDP 14-modified G4 PAMAM dendrimer and LDP 14-modified G4 PAMAM/pEGFP-N1 plasmid complexes) via ObR, energy and species dependent manner (preferred uptake by human/mouse cell lines compared to rat cell line). Importantly, our findings illustrated that the entry of LDP 14-modified dendrimers in hBCEC-D3 cells not only is not affected by protein corona (PC) formation, as the main reason for diminishing the cellular uptake, but also PC per se can enhance uptake rate. Finally, fluorescein labeled LDP 14-modified G4 PAMAM dendrimers efficiently accumulated in the mice brain with lower biodistribution in other organs, in our in vivo study. Conclusion: LDP 14 introduced as a novel and highly efficient ligand, which can be used for drugs/genes delivery to brain tissue in different central nervous system (CNS) disorders.

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.

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, 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A modified TEGDMA-based resin infiltrant using polyurethane acrylate oligomer and remineralising nano-fillers with improved physical properties and remineralisation potential.

OBJECTIVES: This study aimed to modify an experimental triethylene glycol dimethacrylate (TEGDMA) based resin infiltrant using PUA oligomer and two remineralising fillers, including fluorohydroxyapatite (FHA) and fluoride-doped bioactive glass (FD-BG), to improve the mechanical and physical properties and induce remineralising potential. MATERIALS AND METHODS: The polyurethane acrylate oligomer (PUA) was synthesised and characterised. Experimental resin infiltrant was prepared by mixing 10% of synthesised PUA with 88% TEGDMA. Water contact angle, penetration coefficient, and penetration depth were then measured. The FHA and FD-BG fillers were synthesised and characterised. To prepare nano-filled resin infiltrant, 5% of each powder was mixed with the prepared resin infiltrant. The prepared resin infiltrants were characterised to evaluate their degree of conversion, mechanical properties, water sorption, and solubility. The ion release of filled resin was also assessed. The non-infiltrated and infiltrated enamel specimens underwent fourteen days of pH-cycling, and a surface microhardness was done to assess the resistance to demineralisation. RESULTS: The results showed that the addition of PUA to TEGDMA increased the mechanical properties and decreased water sorption and solubility. The addition of synthesised FD-BG fillers to resin infiltrant significantly improved the resistance to demineralisation of enamel samples compared with other groups (p ≤ 0.001). The FHA fillers also improved the resistance to demineralisation; however, the produced changes were not statistically meaningful (p > 0.05). CONCLUSIONS: Based on the results, the PUA+TEGDMA+ FD-BG/FHA composite can be used as an alternative material for pure TEGDMA in enamel infiltration approaches owing to its better mechanical properties, lower water sorption and solubility, and also remineralisation potential. CLINICAL SIGNIFICANCE: A resin infiltrant with remineralisation potential, lower water sorption and solubility and higher mechanical properties may enhance the management of early caries lesions.

Preparation of Polyurethane/Pluronic F127 Nanofibers Containing Peppermint Extract Loaded Gelatin Nanoparticles for Diabetic Wounds Healing: Characterization, In Vitro, and In Vivo Studies.

Diabetic ulcer is regarded as one of the most prevalent chronic diseases. The healing of these ulcers enhances with the use of herbal extracts containing wound dressings with high antibacterial property and creating a nano-sized controlled release system. In this study, new peppermint extract was incorporated in the polyurethane- (PU-) based nanofibers for diabetic wound healing. The peppermint extract was used as an herbal antimicrobial and anti-inflammatory agent. The absorption ability of the wound dressing was enhanced by addition of F127 pluronic into the polymer matrix. The release of the extract was optimized by crosslinking the extract with gelatin nanoparticles (CGN) and their eventual incorporation into the nanofibers. The release of the extract was also controlled through direct addition of the extract into the PU matrix. The results showed that the release of extract from nanofibers was continued during 144 hours. The prepared wound dressing had a maximum absorption of 410.65% and an antibacterial property of 99.9% against Staphylococcus aureus and Escherichia coli bacteria. An in vivo study indicated on significant improving in wound healing after the use of the extract as an effective compound. On day 14, the average healing rate for samples covered by conventional gauze bandage, PU/F127, PU/F/15 (contained extract), and PU/F/15/10 (contained extract and CGN) prepared with different nanoparticle concentrations of 5 and 10 was 47.1 ± 0.2, 56.4 ± 0.4, 65.14 ± 0.2, and 90.55 ± 0.15%, respectively. Histopathological studies indicated that the wound treated with the extract containing nanofibers showed a considerable inflammation reduction at day 14. Additionally, this group showed more resemblance to normal skin with a thin epidermis presence of normal rete ridges and rejuvenation of skin appendages. Neovascularization and collagen deposition were higher in wounds treated with the extract containing nanofibrous wound dressing compared to the other groups.

Fast antibody responses by immuno-targeting and nanotechnology strategies versus HBsAg vaccine.

OBJECTIVES: Though immunization with HBsAg has been routine since the 1980s, it has numerous limitations such as low or none humoral immune responses. Today, nanotechnology is used in vaccinology to achieve higher potency. The present study deals with the achievement of fast antibody response of humoral immune responses using immune-targeting through mannosylated nanocarriers of the vaccine. MATERIALS AND METHODS: Mannose sugar and HBsAg were attached to the surface of iron oxide nanoparticles. Mannosylated iron oxide nanoparticles conjugated HBsAg (HBsAg +MLCMNP), iron oxide nanoparticles conjugated HBsAg (HBsAg +LCMNP), hepatitis B vaccine, and mere HBsAg were injected twice to BALB/c mice subcutaneously, while suitable control groups were considered. Specific total IgG antibodies were evaluated on the 7th and 14th days after the final immunization. The avidity maturation of the humoral immune response was assessed with an optimized ELISA. Graph pad prism software was used to analyze statistical data. RESULTS: Results showed that on the seventh day of the final shooting, the mannosylated nano-vaccine caused higher antibody response induction than nano-vaccine without mannose and commercial vaccine groups. After 14 days of the second injection, a significant difference was seen versus the nano-vaccine without mannose but not the commercial vaccine group. In addition, the avidity index in mannosylated nano-vaccine showed a significant increase compared with the nano-vaccine without mannose and mere HBsAg group but not compared with the commercial vaccine. CONCLUSION: It seems that mannosylated nano-vaccine has more potency to achieve fast antibody responses and also higher quality of humoral immune response.

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.