Physical, Mechanical, and Anti-Biofilm Formation Properties of CAD-CAM Milled or 3D Printed Denture Base Resins: In Vitro Analysis.

PURPOSE: To investigate surface characteristics (roughness and contact angle), anti-biofilm formation, and mechanical properties (mini-flexural strength) of computer-aided design and computer-aided manufacturing (CAD-CAM) polymethylmethacrylate (PMMA) polymer, and three-dimensional (3D) printed resin for denture base fabrication compared with conventional heat polymerized denture base resins. MATERIALS AND METHODS: A total of 60 discs and 40 rectangular specimens were fabricated from one CAD-CAM (AvaDent), one 3D printed (Cosmos Denture), and two conventional heat polymerized (Lucitone 199 and VipiWave) materials for denture base fabrication. Roughness was determined by Ra value; the contact angle was measured by the sessile drop method. The biofilm formation inhibition behavior was analyzed through Candida albicans adhesion, while mini-flexural strength test was done using a three-point bending test. The data were analyzed using descriptive and analytical statistics (α = 0.05). RESULTS: The CAD-CAM PMMA group showed the lowest C. albicans adhesion (log CFU/mL: 3.74 ± 0.57) and highest mini-flexural strength mean (114.96 ± 16.23 MPa). 3D printed specimens presented the highest surface roughness (Ra: 0.317 ± 0.151 µm) and lowest mini-flexural strength values (57.23 ± 9.07 MPa). However, there was no statistical difference between CAD-CAM PMMA and conventional groups for roughness, contact angle, and mini-flexural strength. CONCLUSIONS: CAD-CAM milled materials present surface and mechanical properties similar to conventional resins and show improved behavior in preventing C. albicans adhesion. Nevertheless, 3D printed resins present decreased mini-flexural strength.

Effect of blue light plus chlorhexidine therapy on Streptococcus mutans biofilm and its regrowth in an in vitro orthodontic model.

INTRODUCTION: Fixed orthodontic appliances create areas of stagnation for dental biofilms and make it difficult to clean the teeth; therefore, there is a risk of developing incipient caries lesions during the orthodontic treatment. The objective of this study is to determine if the combination of 2 different therapies, phototherapy by blue light (BL) and the antimicrobial 0.12% chlorhexidine (CHX) on enamel, orthodontic brackets, and elastics, would reduce or inhibit mature Streptococcus mutans biofilms and their regrowth on these substrates 24 hours after the application of the treatment; and if this treatment would interfere with bracket adhesion to the enamel. METHODS: Biofilms of S. mutans UA159 were formed for 5-days over samples composed of a bovine enamel, orthodontic bracket, and orthodontic elastic. Then, the specimens were treated with 0.89% NaCl for 1 minute, BL for 12 minutes (72 J/cm2), 0.12% CHX for 1 minute, and BL for 12 minutes, followed by 0.12% CHX for 1 minute (BL+CHX). Biofilm was evaluated by colonies forming units and dry weight immediately after treatments and 24 hours after treatments (regrowth). The pH of the spent media was measured on the fifth and sixth days. Biofilm formation on the samples after the treatments and regrowth was visually evaluated by confocal laser scanning microscopy. Shear bond strength (SBS) between bracket and enamel was evaluated using a universal testing machine at a crosshead speed of 1 mm/min. After bonding, specimens were thermocycled (500× at 5-55°C), treated, and thermocycled again. RESULTS: After 5 days of biofilm formation, BL+CHX significantly reduced the bacterial viability on enamel compared with NaCl (P = 0.004) and BL (P = 0.014). For bracket and elastic, all the treatments resulted in similar bacterial viability (P ≥0.081). In the regrowth, CHX and BL+CHX significantly reduced the bacterial viability in the enamel compared with the NaCl (P ≤0.015) and BL (P ≤0.013). For bracket, BL+CHX significantly reduced the bacterial viability compared with NaCl (P = 0.008) and BL (P = 0.009). For the elastic, BL+CHX eliminated the biofilms from the substrate. CHX and BL+CHX significantly reduced the bacterial viability 24 hours after treatment for all substrates (P ≤0.05). The media pH significantly increased when samples were treated with CHX and BL+CHX (P ≤0.001). Confocal laser scanning microscopy images visually showed an abundant quantity of red cells in the samples treated with BL+CHX. There was no difference in the SBS between the treatments (P ≥0.932). CONCLUSIONS: The association between BL and CHX reduced S. mutans biofilm and its regrowth on an in vitro orthodontic model and did not influence the bonding strength between bracket and enamel.

Comprehensive biomedical applications of low temperature plasmas.

The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low temperatures and can be activated with noble gases with molecular mixtures or compressed air. LTP reactive species are quickly produced, and are a remarkably good source of reactive oxygen and nitrogen species including singlet oxygen (O2), ozone (O3), hydroxyl radicals (OH), nitrous oxide (NO), and nitrogen dioxide (NO2). Its low gas temperature and highly reactive non-equilibrium chemistry make it appropriate for the alteration of inorganic surfaces and delicate biological systems. Treatment of oral biofilm-related infections, treatment of wounds and skin diseases, assistance in cancer treatment, treatment of viruses' infections (e.g. herpes simplex), and optimization of implants surfaces are included among the extensive plasma medicine applications. Each of these applications will be discussed in this review article.

Saliva proteomics from children with caries at different severity stages.

OBJECTIVE: To perform a comparative analysis of saliva protein profile of patients with early childhood caries at different levels of severity and caries-free individuals. MATERIALS AND METHODS: Stimulated saliva samples were collected from 126 children (2-6 years old), classified according to the ICDAS II, and divided into 3 groups (n = 42): caries-free (CF), enamel caries (EC), and dentine caries (DC). Samples were digested and analyzed by nanoUPLC coupled with a mass spectrometry. Data analyses were conducted with Progenesis QI for Proteomics Software v2.0. Gene Ontology (GO) terms and protein-protein interaction analysis were obtained. RESULTS: A total of 306 proteins (≈6 peptides) were identified. Among them, 122 were differentially expressed in comparisons among children with different caries status. Out of the 122 proteins, the proteins E2AK4 and SH3L2 were exclusively present in groups CF and EC, respectively, and 8 proteins (HAUS4, CAH1, IL36A, IL36G, AIMP1, KLHL8, KLH13, and SAA1) were considered caries-related proteins when compared to caries-free children; they were up-regulated proteins in the caries groups (EC and DC). CONCLUSION: The identification of exclusive proteins for caries-free or carious-related conditions may help in understanding the mechanisms of caries and predicting risk as well as advancing in caries control or anti-caries approaches.

The effects of charcoal dentifrices on Streptococcus mutans biofilm development and enamel demineralization.

PURPOSE: To evaluate the in vitro effects of commercially available charcoal dentifrices on Streptococcus mutans biofilm development and their ability to prevent enamel demineralization. METHODS: Streptococcus mutans biofilm was formed on polished bovine enamel specimens (n= 9 per treatment), and treated twice-daily for 120 seconds over the course of 5 days with: charcoal dentifrice containing fluoride (1,000 ppm F) (CF+), fluoride-free charcoal dentifrice (CF-), regular fluoride (1,100 ppm F) dentifrice (F+ ), or regular fluoride-free dentifrice (F-). Chlorhexidine (CHX, 0.12%) and deionized water (DIW) were used as positive and negative controls, respectively. Biofilms were analyzed for bacterial viability (colony-forming units, CFU). The pH of the medium was measured daily. Enamel specimens were analyzed using Vickers microhardness ( HV) and transversal microradiography (TMR). Data were analyzed using one-way ANOVA followed by post-hoc tests (α= 0.05). RESULTS: F+ showed higher pH values than CF+ and CF-, and CF- presented higher pH than CF+, showing that CF+ did not have inhibitory effects on the acidogenicity of cariogenic biofilms. CFU was significantly decreased when specimens were treated with CF+, CF- and F+, compared to specimens treated with DIW (P≤ 0.035) or F- (P≤ 0.001), respectively. However, the reduction observed was minimal (approximately 1 log). CF+ and CF- were less effective than F+ in preventing enamel demineralization as determined using HV (P= 0.041 and P= 0.003, respectively) and TMR ( P≤ 0.001). Both charcoal dentifrices (CF+, CF-) did not show relevant inhibition of S. mutans biofilm growth. Additionally, neither product prevented enamel demineralization compared to a regular fluoride-containing dentifrice. CLINICAL SIGNIFICANCE: The tested charcoal dentifrices did not exhibit anticaries potential.

Influence of cervical preflaring and root canal preparation on the fracture resistance of endodontically treated teeth.

BACKGROUND: Evaluate the fracture resistance of endodontically treated teeth after cervical preflaring and root canal preparation and to assess the volume of the root canal and the amount of remaining root dentin before and after cervical preflaring. METHODS: Forty-four mandibular incisors were selected using micro-CT scanning and distributed into 4 groups (n = 11) according to the instrument used for cervical preflaring: control group - no cervical preflaring; Gates Glidden - burs size #2 and #3; WXN - 25.07 Navigator instrument; and Easy - 25.08 ProDesign S instrument. Coronal opening was performed, and the canals were prepared with Wave One Gold Primary and filled with an epoxy-resin based sealer and gutta-percha cones. Micro-CT scans were performed before and after root canal instrumentation. All images were reconstructed and assessed for the thickness of mesial and distal root dentin at 3 mm and 5 mm from the cement -enamel junction and for the volume of cervical portion of the canal after preparation. Fracture resistance test was performed applying compressive loads at a crosshead speed of 0.5 mm/min, applied on the palatal aspect of specimens at 135° along the long axis of the tooth. The data were analyzed using ANOVA and Tukey's test (P = .05). RESULTS: Cervical preflaring and canal preparation reduced the dentin thickness (P < .05) and increased the canal volume (P < .05) in all groups at 3 mm an 5 mm. Cervical preflaring with Gates Gliden burs reduced the fracture resistance of endodontically treated teeth (P < .05). CONCLUSIONS: All instruments reduced the dentin thickness and increased the canal volume in the cervical at 3 mm and 5 mm. Gates Glidden reduced fracture resistance of mandibular incisors submitted to cervical preflaring, whereas NiTi instruments did not. CLINICAL RELEVANCE: Cervical preflaring assumes particular importance previously to the root canal preparation because it minimizes the occurrence of operative accidents, and permits more accurate determination of working length and the apical diameter.

Twice-daily red and blue light treatment for Candida albicans biofilm matrix development control.

Phototherapy has been proposed as a direct means of affecting local bacterial infections. However, the use of phototherapy to prevent fungal biofilm development has received comparatively less attention. This study aimed to determine the effects of red light treatment and blue light treatment, without a photosensitizer, on the development of Candida albicans biofilm. During the development of 48-h biofilms of C. albicans SN 425 (n = 10), the biofilms were exposed twice-daily to noncoherent blue and red light (LumaCare; 420 nm and 635 nm). The energy density applied was 72 J cm-2 for blue light and 43.8 J cm2, 87.6 J cm2, and 175.5 J cm2 for red light. Positive control (PC) and negative control (NC) groups were treated twice-daily for 1 min with 0.12% chlorhexidine (CHX) and 0.89% NaCl respectively. Biofilms were analyzed for colony forming units (CFU), dry-weight, and exopolysaccharides (EPS-soluble and EPS-insoluble). Data was analyzed by one-way ANOVA and Tukey post hoc test (α = 0.05). Dry-weight was lower than NC (p < 0.001) and approached PC levels with both red and blue light treatments. CFU were also lower in groups exposed to blue light and higher durations of red light (p < 0.05). EPS-soluble and EPS-insoluble measures were variably reduced by these light exposures. In conclusion, twice-daily exposure to both blue and red lights affect the biofilm development and physiology of polysaccharide production and are potential mechanisms for the control of C. albicans biofilm matrix development.

Estimating potential soil sheet Erosion in a Brazilian semiarid county using USLE, GIS, and remote sensing data.

The present study aimed to estimate soil erosion in Machados County, Brazil. Rainfall erosivity was calculated using monthly and annual precipitation averages over a 30-year interval, soil erodibility was obtained with a granularity-based equation, and topography and land cover were obtained from DEM data and Sentinel - 2B imagery, respectively. A GIS interface was used to spatialize parameter results and for topography and land cover analysis. The achieved results allowed surmising that the soil loss for the study region risk is low, but significant, with a mean value of 8.11 t/ha year. About a quarter of the total area presented high soil loss, above 20 t/ha year. The biggest influential factors were soil erodibility, with a mean value of 0.028, and land cover, averaging 0.1409. The topographic factor averaged 3.414 and rain erosivity, found to be 2747.22 mm/year, is considered low for the region. Given a lack of conservative practices observed during field work, the soil stewarship P factor was considered 1 for the assessment. The use of orbital images to obtain C factor and the expression applied to calculate soil erodibility provided adequate results. In addition, there is a need for research to monitor and quantify erosion processes in Brazilian semiarid, as well as their erosion tolerance.

Short- and Long-term Evaluation of Dentin-Resin Interfaces Formed by Etch-and-Rinse Adhesives on Plasma-treated Dentin.

PURPOSE: To investigate the influence of atmospheric pressure plasma (APP) treatment on the microtensile dentin bond strength of two etch-and-rinse adhesive systems, after one week and one year of water storage, and additionally to observe the micromorphology of resin/dentin interfaces under scanning electronic microscopy (SEM). MATERIALS AND METHODS: The occlusal enamel was removed from third human molars to expose a flat dentin surface. The teeth were then randomly divided into six groups (n = 7), according to two adhesives (Optibond FL and XP-Bond) and three APP treatments (untreated dentin [control], APP application before or after acid etching). After performing the composite resin buildup on bonded dentin, the teeth were sectioned perpendicularly to the bonded interface to obtain beam-shaped specimens (cross-sectional area of ~0.9 mm2). The specimens were tested in tension until failure after one week and one year of water storage (1.0 mm/min rate). Bond strength data were analyzed by three-way ANOVA and Tukey's post-hoc test (α = 0.05%). Bonded beam specimens from each tooth were also prepared for interfacial SEM investigation. RESULTS: At one week, APP treatment applied after acid etching increased the dentin bond strength for XP Bond, while no effect was observed for Optibond FL. After one year, the bond strength of XP Bond decreased in groups where APP was applied after etching. The evaluation time did not influence the bond strength for Optibond FL. CONCLUSION: One-year evaluation did not show any sign of degradation of interfacial structures in any group. Application of APP to etched dentin combined with a two-step etch-and-rinse adhesive significantly increased bond strength at one week, but the effect was not stable after one year and was adhesive dependent.

Photodynamic antimicrobial chemotherapy on Streptococcus mutans using curcumin and toluidine blue activated by a novel LED device.

Photodynamic antimicrobial chemotherapy (PACT) is an antimicrobial approach that uses photosensitizers (PS) in combination with light sources at specific wavelengths aiming the production of reactive oxygen species. The long illumination time necessary to active PS is a challenge in PACT. Thus, this study investigated the antimicrobial effect of a novel single source of light-emitting diode (LED) light that covers the entire spectrum of visible light beyond interchangeable probes at high power intensity. Blue and red LED probes were used into different exposure times to active different concentrations of curcumin (C) and toluidine blue (T) on planktonic suspensions of Streptococcus mutans UA 159 (S. mutans). S. mutans were standardized and submitted to (1) PACT treatment at three concentrations of C and T exposure at three radiant exposures of a blue LED (BL) (C+BL+) and a red LED (RL) (T+RL+), (2) C (C+BL-) or T alone (T+RL-), (3) both LED lights (C-BL+ and T-RL+), and (4) neither PS nor LED illumination (control group: C-BL- and T-RL-). Aliquots of the suspensions were diluted and cultured on blood agar plates. The number of colony-forming units was calculated after 48 h. The groups submitted to PACT presented a lethal photokilling rate to all PS concentrations at tested dosimetries. The comparison to control group when PS and LED lights used alone demonstrated no decrease in the number of viable bacterial counts. The novel LED device in combination with curcumin and toluidine blue promoted an effective photoinactivation of S. mutans suspensions at ultrashort light illumination times.

Morphological changes and viability of Streptococcus mutans biofilm treated with erythrosine: A confocal laser scanning microscopy analysis.

Antimicrobial photodynamic therapy (a-PDT) is a modality that aims to induce microorganisms through visible light, a photosensitizer, and molecular oxygen. This therapy has shown promising results in controlling cariogenic biofilm in vitro and in vivo counterparts. This study investigated bacterial viability and morphological characterization of Streptococcus mutans mature biofilms after combination of erythrosine and a high potency dental curing light. Biofilms were formed on saliva-coated hydroxyapatite disks in batch culture. The samples were performed in triplicates. Fresh medium was replaced daily for five days and treated using 40 µM of E activated by HL 288 J/cm2 and total dose of 226 J at 1200 mW/cm2. Phosphate buffer saline and 0.12% of chlorhexidine were used as negative and positive control, respectively. After treatment, biofilms were assessed for microbial viability and morphological characterization by means of bio-volume and thickness. COMSTAT software was used for image analysis. Data were analyzed using two-way ANOVA followed by Tukey test with significance level 5%. The application of a-PDT and CHX treatments decreased S. mutans bacterial viability. The image analysis showed more red cells on biofilms when compared to other groups, demonstrating photobacterial killing. Erythrosine irradiated with a high potency curing light can potentially act as an antimicrobial tool in the treatment of cariogenic biofilms. The morphology and viability of microorganisms were impacted after treatment. Treatment with photodynamic therapy may be able to reduce the bio-volume and viability of bacteria present in biofilms. CLINICAL RELEVANCE AND RESEARCH HIGHLIGHTS: The use of the a-PDT technique has been applied in dentistry with satisfactory results. Some applications of this technique are in stomatology and endodontics. In the present study, we sought to understand the use of photodynamic therapy in the control of biofilm and the results found are compatible with the objective of microbiological control proposed by this technique, thus raising the alert for future studies in vivo using the combination of a-PDT with erythrosine, since they are easily accessible materials for the dental surgeon and can be applied in clinical practice.

Structure-Metabolism Relationships of benzimidazole derivatives with anti-Trypanosoma cruzi activity for Chagas disease.

This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42e and 49b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.

Structure-activity relationships of novel N-imidazoylpiperazines with potent anti-Trypanosoma cruzi activity.

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.

Evaluation and discovery of novel benzothiazole derivatives as promising hits against Leishmania infantum.

An early exploration of the benzothiazole class against two kinetoplastid parasites, Leishmania infantum and Trypanosoma cruzi, has been performed after the identification of a benzothiazole derivative as a suitable antileishmanial initial hit. The first series of derivatives focused on the acyl fragment of its class, evaluating diverse linear and cyclic, alkyl and aromatic substituents, and identified two other potent compounds, the phenyl and cyclohexyl derivatives. Subsequently, new compounds were designed to assess the impact of the presence of diverse substituents on the benzothiazole ring or the replacement of the endocyclic sulfur by other heteroatoms. All compounds showed relatively low cytotoxicity, resulting in decent selectivity indexes for the most active compounds. Ultimately, the in vitro ADME properties of these compounds were assessed, revealing a satisfying water solubility, gastrointestinal permeability, despite their low metabolic stability and high lipophilicity. Consequently, compounds 5 and 6 were identified as promising hits for further hit-to-lead exploration within this benzothiazole class against L. infantum, thus providing promising starting points for the development of antileishmanial candidates.

Comparison of In Vitro Biofilm Formation on Titanium and Zirconia Implants.

Background: Peri-implant diseases are emerging issues in contemporary implant dentistry. As biofilms play a critical role in peri-implant diseases, the characteristic of resisting bacterial adhesion would be ideal for dental implants. The aims of the study were to compare titanium (Ti) and zirconia (Zr) implants regarding the amount of biofilm formation at different time frames and assess the distribution of biofilm on different aspects of dental implants. Methods: Biofilm was developed on Ti and Zr dental implants with a peri-implant-related multispecies model with Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar, and Porphyromonas gingivalis, for 3 and 14 days. Quantitative assessment was performed with the measurement of total bacterial viability (colony forming units, CFU/mg). Scanning electron microscopy (SEM) was used to evaluate biofilm formation on different aspects of the implants. Results: Three-day-old biofilm on Ti implants was significantly higher than that on Zr implants (p < 0.001). The Ti and Zr groups were not significantly different for 14-day-old biofilm. SEM images demonstrated that 3-day-old biofilm on Zr implants was sparse while biofilm growth was more pronounced for 3-day-old biofilm on Ti implants and 14-day-old biofilm groups. It appeared that less biofilm formed on the valley compared to the thread top for 3-day-old biofilm on Zr implants. Differences between the valley and the thread top became indistinguishable with the development of mature biofilm. Conclusion: While early formed biofilms show greater accumulation on Ti implants compared to Zr implants, older biofilms between the two groups are comparable. The distribution of biofilms was not uniform on different areas of implant threads during early biofilm development.

Effect of titanium dioxide on Streptococcus mutans biofilm.

BACKGROUND: Streptococcus mutans (S. mutans) participates in the dental caries process. Titanium dioxide (TiO2) nanoparticles produce reactive oxygen species capable of disrupting bacterial DNA synthesis by creating pores in cell walls and membranes. OBJECTIVE: The objective of this study was to determine the effect of TiO2 on the disruption of S. mutans biofilm. METHODS: This study was conducted in four phases involving a TiO2-containing toothbrush and TiO2 nanoparticles. Each phase was completed using 24 h established S. mutans biofilm growth. Phase one data was collected through a bacterial plating study, assessing biofilm viability. Biofilm mass was evaluated in phase two of the study by measuring S. mutans biofilm grown on microtiter plates following crystal violet staining. The third phase of the study involved a generalized oxygen radical assay to determine the relative amount of oxygen radicals released intracellularly. Phase four of the study included the measurement of insoluble glucan/extracellular polysaccharide (EPS) synthesis using a phenol-sulfuric acid assay. RESULTS: Both exposure time and time intervals had a significant effect on bacterial viability counts (p = 0.0323 and p = 0.0014, respectively). Bacterial counts after 6 min of exposure were significantly lower than after 2 min (p = 0.034), compared to the no treatment control (p = 0.0056). As exposure time increased, the amount of remaining biofilm mass was statistically lower than the no treatment control. Exposure time had a significant effect on oxygen radical production. Both the 30 and 100 nm TiO2 nanoparticles had a significant effect on bacterial mass. The silver nanoparticles and the 30 and 100 nm TiO2 nanoparticles significantly inhibited EPS production. CONCLUSION: The TiO2-containing toothbrush kills, disrupts, and produces oxygen radicals that disrupt established S. mutans biofilm. TiO2 and silver nanoparticles inhibit EPS production and reduce biofilm mass. The addition of TiO2 to dental products may be effective in reducing cariogenic dental biofilm.

Hit-to-lead optimization of a 2-aminobenzimidazole series as new candidates for chagas disease.

Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Because current treatments present several limitations, including long duration, variable efficacy and serious side effects, there is an urgent need to explore new antitrypanosomal drugs. The present study describes the hit-to-lead optimization of a 2-aminobenzimidazole hit 1 identified through in vitro phenotypic screening of a chemical library against intracellular Trypanosoma cruzi amastigotes, which focused on optimizing potency, selectivity, microsomal stability and lipophilicity. Multiparametric Structure-Activity Relationships were investigated using a set of 277 derivatives. Although the physicochemical and biological properties of the initial hits were improved, a combination of low kinetic solubility and in vitro cytotoxicity against mammalian cells prevented progression of the best compounds to an efficacy study using a mouse model of Chagas disease.

Impact of curcumin loading on the physicochemical, mechanical and antimicrobial properties of a methacrylate-based experimental dental resin.

Oral biofilms are directly linked to one of the most common chronic human diseases, dental caries. Resin-based dental materials have significant potential to replace amalgam, however they lack sufficient antimicrobial power. This innovative study investigates a curcumin-loaded dental resin which can be utilized in an antimicrobial photodynamic therapy (aPDT) approach. The study evaluated the effects of curcumin loading on resin physicochemical, mechanical, and adhesive properties, as well as the antimicrobial response associated with blue light activation. Preliminary tests involving degree of conversion (DC) and sample integrity determined the optimal loading of curcumin to be restricted to 0.05 and 0.10 wt%. These optimal loadings were tested for flexural strength (FS), water sorption (WS) and solubility (SL), shear bond strength to dentin (SBS), and viability of Streptococcus mutans under 14.6 J/cm2 blue light or dark conditions, in 6 h and 24 h biofilms. The results demonstrated that 0.10 wt% curcumin had minimal impact on either FS or SBS, but detectably increased WS and SL. A 2 log10 (CFU/mL) reduction in S. mutans after light application in both 6 h and 24 h biofilms were corroborated by CLSM imaging and highlighted the significant potential of this novel aPDT approach with resin-based dental materials.

Effect of curcumin-loaded photoactivatable polymeric nanoparticle on peri-implantitis-related biofilm.

Curcumin has been used as a photosensitizer (PS) for antimicrobial photodynamic chemotherapy (PACT). However, its low solubility, instability, and poor bioavailability challenge its in vivo application. This study aimed to synthesize curcumin-loaded polymeric nanoparticles (curcumin-NP) and determine their antimicrobial and cytotoxic effects. Nanoparticles (NP) were synthesized using polycaprolactone (PCL) as a polymer by the nanoprecipitation method. Curcumin-NP was characterized by particle size, polydispersity index and zeta potential, scanning electron microscopy, and curcumin encapsulation efficiency (EE). Curcumin-NP was compared to free curcumin solubilized in 10% DMSO as photosensitizers for PACT in single and multispecies Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus oralis biofilms. Chlorhexidine 0.12% (CHX) and ultrapure water were used as positive and negative controls. The cytotoxic effect of curcumin-NP was evaluated on human periodontal ligament fibroblast cells (HPLF). Data were analyzed by ANOVA (α=0.05). Curcumin-NP exhibited homogeneity and stability in solution, small particle size, and 67.5% EE of curcumin. Curcumin-NP presented reduced antibiofilm activity at 500 µg/ml, although in planktonic cultures it showed inhibitory and bactericidal effect. Curcumin-NP and curcumin with and without photoactivation were not cytotoxic to HPLF cells. Curcumin-NP has antimicrobial and antibiofilm properties, with better effects when associated with blue light, being a promising therapy for preventing and treating peri-implant diseases.

In-vitro evaluation of the anti-cariogenic effect of a hybrid coating associated with encapsulated sodium fluoride and stannous chloride in nanoclays on enamel.

OBJECTIVE: The aim of this study is to test, in vitro, the anti-cariogenic effect of experimental hybrid coatings, with nano clays of halloysite or bentonite, loaded with sodium fluoride or with a combination of sodium fluoride and stannous chloride, respectively. METHODOLOGY: The varnish Fluor Protector (1,000 ppm of F-) was used as positive control and no treatment was the negative control. Enamel specimens (5 mm × 5 mm) were obtained from bovine teeth. The specimens (n=10) had their surfaces divided into two halves (5 mm × 2.5 mm each), in which one half received one of the treatments (Hybrid; Hybrid + NaF; Hybrid + NaF + SnCl2; Hybrid + NaF Loaded; Hybrid + NaF + SnCl2 Loaded). The specimens were submitted to a cariogenic challenge using a biofilm model (S. mutans UA159, for 5 days). Enamel surfaces both under and adjacent to the treated area were analyzed for mineral loss and lesion depth, by transverse microradiography. The pH of the medium was measured twice a day, and the fluoride release was analyzed. Additional specimens were submitted to confocal analysis. RESULTS: Data were statistically analyzed by two-way ANOVA followed by Tukey test (α=0.05). None of hybrid groups were able to reduce the lesion depth; the Hybrid + NaF group, however, was able to reduce mineral loss differing from the negative control (p=0.008). The groups showed no significant difference in the pH measurement and fluoride release. Confocal analysis confirmed that for all groups the biofilm growth was similar. CONCLUSION: None of the hybrid groups reduced lesion depth, but the Hybrid + NaF group was able to promote protection against mineral loss.