Bacterial resistance to antimicrobial photodynamic therapy: A critical update.

Bacterial antibiotic resistance is one of the most significant challenges for public health. The increase in bacterial resistance, mainly due to microorganisms harmful to health, and the need to search for alternative treatments to contain infections that cannot be treated by conventional antibiotic therapy has been aroused. An alternative widely studied in recent decades is antimicrobial photodynamic therapy (aPDT), a treatment that can eliminate microorganisms through oxidative stress. Although this therapy has shown satisfactory results in infection control, it is still controversial in the scientific community whether bacteria manage to develop resistance after successive applications of aPDT. Thus, this work provides an overview of the articles that performed successive aPDT applications in models using bacteria published since 2010, focusing on sublethal dose cycles, highlighting the main PSs tested, and addressing the possible mechanisms for developing tolerance or resistance to aPDT, such as efflux pumps, biofilm formation, OxyR and SoxRS systems, catalase and superoxide dismutase enzymes and quorum sensing.

Nanocarriers for photodynamic-gene therapy.

The use of nanotechnology in medicine has important potential applications, including in anticancer strategies. Nanomedicine has made it possible to overcome the limitations of conventional monotherapies, in addition to improving therapeutic results by means of synergistic or cumulative effects. A highlight is the combination of gene therapy (GT) and photodynamic therapy (PDT), which are alternative anticancer approaches that have attracted attention in the last decade. In this review, strategies involving the combination of PDT and GT will be discussed, together with the role of nanocarriers (nonviral vectors) in this synergistic therapeutic approach, including aspects related to the design of nanomaterials, responsiveness, the interaction of the nanomaterial with the biological environment, and anticancer performance in studies in vitro and in vivo.

Photodynamic Therapy Can Modulate the Nasopharyngeal Carcinoma Microenvironment Infected with the Epstein-Barr Virus: A Systematic Review and Meta-Analysis.

Nasopharyngeal carcinoma is a malignancy from epithelial cells predominantly associated with the Epstein-Barr virus (EBV) infection, and it is responsible for 140,000 deaths annually. There is a current need to develop new strategies to increase the efficacy of antineoplastic treatment and reduce side effects. Thus, the present study aimed to perform a systematic review and meta-analysis of the ability of photodynamic therapy (PDT) to modulate the tumor microenvironment and PDT efficacy in nasopharyngeal carcinoma treatment. The reviewers conducted all steps in the systematic review. PubMed, Science Direct, Scopus, Scielo, Lilacs, EMBASE, and the Cochrane library databases were searched. The OHAT was used to assess the risk of bias. Meta-analysis was performed with a random-effects model (α = 0.05). Nasopharyngeal carcinoma cells treated with PDT showed that IL-8, IL-1α, IL-1ß, LC3BI, LC3BII, MMP2, and MMP9 levels were significantly higher than in groups that did not receive PDT. NF-ĸB, miR BART 1-5p, BART 16, and BART 17-5p levels were significantly lower in the PDT group than in the control group. Apoptosis levels and the viability of nasopharyngeal carcinoma cells (>70%) infected with EBV were effective after PDT. This treatment also increased LMP1 levels (0.28-0.50/p < 0.05) compared to the control group. PDT showed promising results for efficacy in killing nasopharyngeal carcinoma cells infected with EBV and modulating the tumor microenvironment. Further preclinical studies should be performed to validate these results.

Potential Use of Brazilian Green Propolis Extracts as New Photosensitizers for Antimicrobial Photodynamic Therapy against Cariogenic Microorganisms.

The synergic effect of Streptococcus mutans and Candida albicans increases dental caries severity. Antimicrobial photodynamic therapy (aPDT) is a non-invasive treatment for antimicrobial aspects. However, the current photosensitizers (PS) have many downsides for dental applications. This study aimed to evaluate the efficiency of two different Brazilian green propolis (BGP-AF and BGP-AG) as PS for aPDT against these microorganisms. A single-species biofilm was irradiated with crude extracts and their fractions and controls. Such extracts showed the best results and were evaluated in dual-species biofilms. Photodegradation, reactive oxygen species (ROS), cytotoxicity, and color stability assays were also investigated. Reductions higher than 3 log10 CFU/mL (p < 0.0001) occurred for crude BGP in single- and dual-species biofilms. Singlet oxygen was produced in BGP (p < 0.0001). BGP-mediated aPDT delayed S. mutans and C. albicans regrowth after 24 h of treatment (p < 0.0001). Both BGP did not change the color of dental materials (p > 0.05). BGP-AF-mediated aPDT showed 72.41% of oral keratinocyte viability (p < 0.0001). BGP extracts may be used in aPDT against S. mutans and C. albicans. Specifically, BGP-AF may represent a promising PS for dental applications.

In Vitro Evaluation of Photodynamic Activity of Plant Extracts from Senna Species against Microorganisms of Medical and Dental Interest.

Background: Bacterial resistance requires new treatments for infections. In this context, antimicrobial photodynamic therapy (aPDT) is an effective and promising option. Objectives: Three plant extracts (Senna splendida, Senna alata, and Senna macranthera) were evaluated as photosensitizers for aPDT. Methods: Cutibacterium acnes (ATCC 6919), Streptococcus mutans (ATCC 35668), Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028) were evaluated. Reactive oxygen species production was also verified. Oral keratinocytes assessed cytotoxicity. LC-DAD-MS analysis identified the chemical components of the evaluated extracts. Results: Most species cultured in the planktonic phase showed total microbial reduction (>6 log10 CFU/mL/p < 0.0001) for all extracts. C. albicans cultured in biofilm showed total microbial reduction (7.68 log10 CFU/mL/p < 0.0001) for aPDT mediated by all extracts. Extracts from S. macranthera and S. alata produced the highest number of reactive oxygen species (p < 0.0001). The S. alata extract had the highest cell viability. The LC-DAD-MS analysis of active extracts showed one naphthopyrone and seven anthraquinones as potential candidates for photoactive compounds. Conclusion: This study showed that aPDT mediated by Senna spp. was efficient in microbial suspension and biofilm of microorganisms of medical and dental interest.

Assessment of synergism between enzyme inhibition of Cu/Zn-SOD and antimicrobial photodynamic therapy in suspension and E. coli biofilm.

BACKGROUND: Antimicrobial Photodynamic Therapy (aPDT) is a treatment based on the interaction between a photosensitizer (PS), oxygen and a light source, resulting in the production of reactive oxygen species (ROS). There are two main types of reactions that can be triggered by this interaction: type I reaction, which can result in the production of hydrogen peroxide, superoxide anion and hydroxyl radical, and type II reaction, which is the Photodynamic Reaction, which results in singlet oxygen production. Antioxidant enzymes (e.g., catalase and superoxide dismutase) are agents that help prevent the damage caused by ROS and, consequently, reduce the effectiveness of aPDT. The aim of this study was to evaluate a possible synergism of the combined inhibition therapy of the enzyme Cu/Zn-Superoxide dismutase (SOD) and the methylene blue- and curcumin-mediated aPDT against Escherichia coli ATCC 25922, in suspension and biofilm. METHODS: Kinetic assay of antimicrobial activity of diethydithiocarbamate (DDC) and Minimum Bactericidal Concentration (MIC) of DDC were performed to evaluate the behavior of the compound on bacterial suspension. Inhibition times of Cu/Zn-SOD, as well as DDC concentration, were evaluated via bacterial susceptibility to combined therapy in suspension and biofilm. RESULTS: DDC did not present MIC at the evaluated concentrations. The inhibition time and Cu/Zn-SOD concentration with the highest bacterial reductions were 30 minutes and 1.2 µg/mL, respectively. Synergism occurred between DDC and MB-mediated aPDT, but not with CUR-mediated aPDT. CONCLUSIONS: The synergism between Cu/Zn-SOD inhibition and aPDT has been confirmed, opening up a new field of study full of possibilities.

Photodynamic therapy for treating infected skin wounds: A systematic review and meta-analysis from randomized clinical trials.

BACKGROUND: Infected skin wounds represent a public health problem that effects 20 million people worldwide. Photodynamic therapy (PDT) is a treatment option with excellent results against several infections. OBJECTIVE: This study aimed to perform a systematic review and meta-analysis on PDT efficacy for treating infected wounds based on randomized clinical trials (RCTs). METHODS: PubMed, Scopus, Web of Science, SciELO, and the Cochrane library were searched. The Delphi List criteria and the Revised Cochrane risk-of-bias (Rob 2) were used for evaluating the quality of clinical trials. Meta-analyses were performed with the random-effect model. The odds ratio was the effect measure for binary outcomes, while the standard mean difference was used for continuous outcomes. The trim-and-fill method was used to detect small-study effects. The quality of evidence was verified for each outcome. RESULTS: Only four out of 573 articles were selected for the qualitative and quantitative analyses. The most frequent cause of infected wounds was impaired venous circulation (75%). All studies used red LED light. PDT reduced healing time and improved the healing process and wound oxygenation. Patients treated with PDT showed 15% to 17% (p = 0.0003/ I2=0%) lower microbial cell viability in the wound and a significantly smaller wound size (0.72 cm2/p = 0.0187/I2=0%) than patients treated with placebo or red-light exposure. There was a high level of evidence for each meta-analysis outcome. CONCLUSION: PDT can be an excellent alternative treatment for infected skin wounds, though larger trials are needed.

Efficacy of the combination of P5 peptide and photodynamic therapy mediated by bixin and chlorin-e6 against Cutibacterium acnes biofilm.

In this study, the action of antimicrobial peptide (AMP) P5 and antimicrobial photodynamic therapy (aPDT) mediated by bixin and chlorin-e6 (Ce6) on Cutibacterium acnes (C. acnes) in planktonic phase and biofilm were evaluated both as monotherapies and combined therapies. Microbial viability after treatments were quantified by colony-forming units per milliliter of the sample (CFU/mL) and have demonstrated that all treatments employed exerted bactericidal activity, reducing the microbial load by more than 3 log10 CFU/mL, also demonstrating for the first time in the literature the antimicrobial photodynamic effect of bixin that occurs mostly through type I mechanism which was proved by the quantification of superoxide anion production. Bacterial biofilm was completely eliminated only after its exposure to aPDT mediated by this PS, however, Ce6 proved to be a more efficient PS, considering that most of the photodynamic effect of bixin- aPDT was exerted by excitation of the endogenous C porphyrins of C. acnes with blue light. The combination of P5 with Ce6-aPDT showed a synergistic effect on the bacterial biofilm with a reduction in microbial load by more than 10 log10 CFU/mL, in which the ability of P5 to permeabilize the polymeric extracellular matrix of the biofilm explains the obtained results, with greater internalization of the PS as shown by the Confocal Laser Scanning Microscopy. One-way ANOVA (Analysis of Variance) with Tukey's post-test and two-way ANOVA with Bonferroni's post-test were used to compare the values of continuous variables between the control group and the treatment groups.

Solid Dispersions Incorporated into PVP Films for the Controlled Release of Trans-Resveratrol: Development, Physicochemical and In Vitro Characterizations and In Vivo Cutaneous Anti-Inflammatory Evaluation.

Trans-resveratrol can promote various dermatological effects. However, its high crystallinity decreases its solubility and bioavailability. Therefore, solid dispersions have been developed to promote its amorphization; even so, they present as powders, making cutaneous controlled drug delivery unfeasible and an alternative necessary for their incorporation into other systems. Thus, polyvinylpyrrolidone (PVP) films were chosen with the aim of developing a controlled delivery system to treat inflammation and bacterial infections associated with atopic dermatitis. Four formulations were developed: two with solid dispersions (and trans-resveratrol) and two as controls. The films presented with uniformity, as well as bioadhesive and good barrier properties. X-ray diffraction showed that trans-resveratrol did not recrystallize. Fourier-transform infrared spectroscopy (FT-IR) and thermal analysis evidenced good chemical compatibilities. The in vitro release assay showed release values from 82.27 ± 2.60 to 92.81 ± 2.50% (being a prolonged release). In the in vitro retention assay, trans-resveratrol was retained in the skin, over 24 h, from 42.88 to 53.28%. They also had low cytotoxicity over fibroblasts. The in vivo assay showed a reduction in inflammation up to 66%. The films also avoided Staphylococcus aureus's growth, which worsens atopic dermatitis. According to the results, the developed system is suitable for drug delivery and capable of simultaneously treating inflammation and infections related to atopic dermatitis.

Effect of the technique of photodynamic therapy against the main microorganisms responsible for periodontitis: A systematic review of in-vitro studies.

OBJECTIVE: The present study aimed to conduct a systematic review of the literature, to evaluate, in vitro, the effectiveness of the technique of photodynamic therapy against microorganisms associated with periodontal disease. DESIGN: This systematic review was carried out in accordance with the items on the PRISMA checklist and Cochrane guidelines. Only in vitro studies that evaluated the effect of the technique of antimicrobial photodynamic therapy on periodontopathogenic microorganisms were included. RESULTS: A total of 32 articles published between 2000 and 2021 were included for qualitative analysis. For microorganisms in suspension, 25 studies (78.12%) showed a reduction greater than or equal to 3 logs CFU/mL of species associated with periodontal disease. In biofilms, three studies (42.7%) showed a reduction greater than or equal to 3 logs CFU/mL. CONCLUSIONS: The results showed that the technique of photodynamic therapy may be a promising alternative to conventional antimicrobial approaches for reducing bacteria closely associated with periodontal disease. Some parameters (pre-irradiation time, type of photosensitizer, standardization of light parameters) need to be better established before conducting clinical studies.

Photodynamic therapy associated with nanomedicine strategies for treatment of human squamous cell carcinoma: A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted about photodynamic therapy (PDT) associated with nanomedicine approaches in the treatment of human squamous cell carcinoma (HSSC). Independent reviewers conducted all steps in the systematic review. For evaluating the risk of bias, RoB 2, OHAT and SYRCLE tools were used. Meta-analysis was performed using a random-effect model (α = 0.05). For PDT against HSSC, Protoporphyrin IX was the photosensitizer, and liposomes were the nanomaterial more frequently used. Photosensitizers conjugated with nanoparticles exhibited positive results against HSSC. Tumors treated with PDT in combination with a nanotechnology drug-delivery system had an increased capacity for inhibiting the tumor growth rate (51.93%/P < 0.0001) when compared with PDT only. Thus, the PDT associated with nanomedicine approaches against HSCC could be a significant option for use in future clinical studies, particularly due to improved results in tumor growth inhibition.

Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro.

BACKGROUND: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. METHODS AND RESULTS: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g-1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. CONCLUSION: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms.

Dermatophytes, fungi that cause dermatophytosis, can invade keratinized tissues in humans and animals. The biofilm-forming ability of these fungi was described recently, and it may be correlated with the long treatment period and common recurrences of this mycosis. In this study, we evaluated the anti-dermatophytic and anti-biofilm activity of 2-hydroxychalcone (2-chalcone) in the dark and photodynamic therapy (PDT)-mediated and to determine its mechanism of action. Trichophyton rubrum and Trichophyton mentagrophytes strains were used in the study. The antifungal susceptibility test of planktonic cells, early-stage biofilms, and mature biofilms were performed using colorimetric methods. Topographies were visualized by scanning electron microscopy (SEM). Human skin keratinocyte (HaCat) monolayers were also used in the cytotoxicity assays. The mechanisms of action of 2-chalcone in the dark and under photoexcitation were investigated using confocal microscopy and the quantification of ergosterol, reactive oxygen species (ROS), and death induction by apoptosis/necrosis. All strains, in the planktonic form, were inhibited after treatment with 2-chalcone (minimum inhibitory concentration (MIC) = 7.8-15.6 mg/L), terbinafine (TRB) (MIC = 0.008-0.03 mg/L), and fluconazole (FLZ) (1-512 mg/L). Early-stage biofilm and mature biofilms were inhibited by 2-chalcone at concentrations of 15.6 mg/L and 31.2 mg/L in all tested strains. However, mature biofilms were resistant to all the antifungal drugs tested. When planktonic cells and biofilms (early-stage and mature) were treated with 2-chalcone-mediated PDT, the inhibitory concentrations were reduced by four times (2-7.8 mg/L). SEM images of biofilms treated with 2-chalcone showed cell wall collapse, resulting from a probable extravasation of cytoplasmic content. The toxicity of 2-chalcone in HaCat cells showed higher IC50 values in the dark than under photoexcitation. Further, 2-chalcone targets ergosterol in the cell and promotes the generation of ROS, resulting in cell death by apoptosis and necrosis. Overall, 2-chalcone-mediated PDT is a promising and safe drug candidate against dermatophytes, particularly in anti-biofilm treatment.

A systematic review and meta-analysis of the effect of photodynamic therapy for the treatment of oral mucositis.

BACKGROUND: Oral mucositis is a significant reaction to antineoplastic treatment characterized with pain, nutritional compromise, impact on the quality of life, interruption in cancer therapy and risk for infection. There is no effective standard protocol for the treatment of oral mucositis. This study aims to synthesize the scientific evidence available about the effects of photodynamic therapy on treatment of oral mucositis. METHODS: PubMed, Scopus, Web of Science, Science Direct, Scielo, Embase and Cochrane libraries were searched. Two independent and calibrated researchers (kappa = 0.92) performed all systematic steps according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To access the risk of bias, RoB 2 and Delphi list criteria for clinical trials were used. Meta-analysis was conducted using the R software with "META" package. RESULTS: Clinical and randomized clinical trials were included with a total of five articles. Meta-analysis, level of evidence, and risk of bias assessment were performed showing that photodynamic therapy was effective in reducing healing time in association with low-power laser therapy when compared to low-power laser therapy alone (p = 0.0005). CONCLUSION: Photodynamic therapy presents promising results for the treatment of oral mucositis. It may be an effective therapeutic option, contributing to the healing of injured tissues especially in the time needed for repair.

Understanding the mechanism of action of peptide (p-BthTX-I)2 derived from C-terminal region of phospholipase A2 (PLA2)-like bothropstoxin-I on Gram-positive and Gram-negative bacteria.

Based on the antimicrobial activity of bothropstoxin-I (BthTX-I) and on the premise that a C-terminal peptide of Lys49 myotoxin can reproduce the antimicrobial activity of the parent protein, we aimed to study the mechanism of action of a peptide derived from the C-terminal region of the myotoxin BthTX-I [(p-BthTX-I)2, sequence: KKYRYHLKPFCKK, disulfide-linked dimer] against Gram-positive and Gram-negative bacteria. Fluorescence quenching technique showed that the carboxyfluorescein labeled-peptide [CF-(p-BthTX-I)2] when incubated with E. coli displayed a superior penetration activity than when incubated with S. aureus. Cell death induced by the peptide (p-BthTX-I)2 showed a loss of membrane integrity in E. coli and S. aureus; however, the mechanisms of cell death were different, characterized by the presence of necrosis-like and apoptosis-like deaths, respectively. Scanning electron microscopy studies in E. coli and S. aureus showed morphological changes in the cells, with superficial deformities, appearance of wrinkles and bubbles, and formation of vesicles. Our results demonstrate that the mechanism of action of the peptide (p-BthTX-I)2 is different in Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Knowledge of the mechanism of action of these peptides is important, since they are promising prototypes for new antimicrobial drugs.

Current applications of drug delivery nanosystems associated with antimicrobial photodynamic therapy for oral infections.

The oral cavity is colonized by several species of microorganisms that can cause dental caries, periodontal diseases, candidiasis, endodontic infections, and, among other diseases related to the dental field. Conventional treatment consists of mechanical removal associated with systemic administration of antimicrobials, which can cause various side effects and microbial resistance. In this context, alternative therapies have been developed, including Antimicrobial Photodynamic Therapy (aPDT). For the improvement of therapy, the implementation of nanotechnology is very important to optimize the delivery system of the dyes or photosensitizers on biological targets. Besides, this combination provides a non-invasive treatment, better solubility and bioavailability, delivery to the target site, controlled release and protection against external and physical-chemical factors, low side effects, and, unlikely resistant species. Although, there are numerous researches on aPDT and nanotechnology, few review articles based on the combination of these three aspects: nanosystems, aPDT and oral infections are available. For this reason, this article aims to discuss the advances and advantages of this combination. Therefore, this article was divided into different types of nanosystems (organic and inorganic nanoparticles) associated with aPDT bringing a description of it is definitions, properties, and, applications in oral infections.

Conjugation of superparamagnetic iron oxide nanoparticles and curcumin photosensitizer to assist in photodynamic therapy.

In this work, we describe the synthesis and characterization of the SPIONP-CUR conjugate between curcumin (CUR) and superparamagnetic iron oxide nanoparticles (SPIONPs), in addition to its application in photodynamic therapy (PDT) using a protocol free of organic solvents as a dispersant. The SPIONP-CUR conjugate was characterized by X-ray diffraction, transmission electron microscopy, zeta potential measurements, Fourier transform infrared spectroscopy, thermogravimetry, magnetometry and magnetic hyperthermia assays. The SPIONP-CUR conjugation occurred by bonding between the keto-enol moiety of CUR and the iron atoms present on the surfaces of the SPIONPs. The conjugate showed heating power under an alternating magnetic field (AMF) and photodynamic action when irradiated with blue LED light. In experiments using PDT against Staphylococcus aureus in the planktonic phase, it was demonstrated that with application of blue light at 3.12 J cm-2, the conjugate (dispersed in water) caused a total reduction of the bacterial load. In the absence of light, the reduction was insignificant, even after 24 h of contact with the bacteria.

Influence of light intensity and irradiation mode on methylene blue, chlorin-e6 and curcumin-mediated photodynamic therapy against Enterococcus faecalis.

This study aimed to evaluate the effect of the continuous irradiation with low intensity (continuous mode) and fractioned irradiation with high intensity (fractionated mode), keeping the same dose of light by using Light Emitting Diode (LEDs) with wavelength emission centered at 450 and at 660 nm, using methylene blue (MB), chlorin-e6 (Ce6) and curcumin (CUR) as photosensitizers (PSs) against planktonic phase of E. faecalis. Cell viability was assessed by counting colonies forming per mL (CFU/mL), and the quantification of reactive species was performed by fluorescence with the photodegradation rate evaluated by measurements of absorbance of PSs at different times. The results revealed that MB-mediated PDT was efficient to achieve total microbial load reduction in both irradiation modes, but in fractional mode it was possible to use a lower light dose. Using Ce6, a total bacterial reduction was observed when fractional light was used, but at the same light dose, there was no reduction in the continuous irradiation mode. CUR-mediated PDT under continuous irradiation mode promoted the total microbial load reduction. However, for fractional mode, a higher concentration of CUR was required to completely reduce E. faecalis cell viability. Our results suggest that the biological response to PDT is variable depending on the irradiation mode and on the photosensitizer. Therefore, these studies indicate that the irradiation mode, intensity and the specific PSs should be taken into account for the development of clinical protocols for PDT.

Inhibitory Effect of a KSL-W Peptide-Loaded Poloxamer 407-Based Microemulsions for Buccal Delivery on Fusobacterium nucleatum Biofilm.

KSL-W peptide has demonstrated antibacterial and antifungal activity and inhibitory effects against oral biofilm. This study aimed to check out the effect of chlorhexidine (CLX) or KSL-W peptide-loaded poloxamer 407-based microemulsions for buccal delivery on Fusobacterium nucleatum (F. nucleatum) biofilm. The formulation (F) containing 10% copolymer poloxamer 407 dispersion (1%), 40% oleic acid and 50% PPG-5-CETETH-20 was characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, bioadhesive and syringeability; and in the treatment of a biofilm produced by F. nucleatum. The darkfield images obtained by PLM and the SAXS curves with an extended peak indicated that the system was characteristic of microemulsions. In a continuous analysis, microemulsions exhibited Newtonian behavior. In frequency, the oscillatory analysis profile presented predominantly viscous behavior. Bioadhesive force detected in the analysis of F (7.4 ± 1.81 mN˙ s) and syringeability (17.83± 5.97 N · mm) being adequate values for buccal administration. After 4 h, KSL-W-loaded F shown over 20% higher effectiveness than chlorhexidine-loaded microemulsions. In conclusion, the KSL-W-loaded microemulsions showed a considerable reduction in F. nucleatum biofilm formation and presented promising structural properties for buccal drug delivery.

Antimicrobial photodynamic therapy against metronidazole-resistant dental plaque bactéria.

The antimicrobial photodynamic therapy (aPDT) has stood out as an alternative and promising method of disinfection and has been exploited for the treatment of oral bacteria. In this study, we evaluate in vitro the action of aPDT, mediated by methylene blue, chlorin-e6, and curcumin against clinical subgingival plaques that were resistant to metronidazole. The sensitivity profile of the samples to metronidazole was analyzed by the agar dilution method. Cell viability in the planktonic and biofilm phase was assessed by CFU / mL. The composition of the biofilm was evaluated by the checkboard DNA-DNA Hibrydization technique. Photosensitizers internalization was qualitatively assessed by confocal fluorescence microscopy (CLSM). The aPDT mediated by the three photosensitizers tested was able to reduce the totality of the planktonic microbial load and partially reduce the biofilm samples. The analysis performed by CLSM showed that the photosensitizers used in the application of aPDT were able to permeate the interior of the biofilm. The aPDT has been shown to be useful in a supportive and effective approach to the treatment of periodontal disease.