Antimicrobial Photodynamic Therapy Research Articles

A coating strategy on titanium implants with enhanced photodynamic therapy and CO-based gas therapy for bacterial killing and inflammation regulation

Antimicrobial photodynamic therapy (aPDT) has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis, especially the aPDT triggered by near-infrared (NIR) light due to the large penetration depth in tissue. However, the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application. Due to the long lifespan and transmission distance of therapeutic gas molecules, we design a multi-functional gas generator that combines aPDT as well as O2 and CO gas release function, which can solve the problem of hypoxia (O2) in PDT and the problem of inflammation regulation (CO) in the distal part of peri‑implant inflammation under near-infrared (NIR) irradiation. In the composite nanoplatform that spin-coated on the surface of titanium implants, up-conversion nanoparticles (UCNPs) were involved in converting the NIR to visible, which further excites the partially oxidized stannic sulfide (SnS2), realizing the therapeutic gas release. Indocyanine green (ICG) was further integrated to enhance the aPDT performance (Ti-U@SnS2/I). Therefore, reactive oxygen species (ROS), CO, and O2 can be controllably administered via a composite nano-platform mediated by a single NIR light (808 nm). This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions, such as relieving the anoxic microenvironment and reaching deep infection sites, providing a viable antibiotic-free technique to combat peri‑implantitis.

Fast Fabrication of Multifunctional PCL/Curcumin Nanofibrous Membranes for Wound Dressings.

Therapeutic intervention to skin wounds requires covering the affected area with wound dressings. Interdisciplinary efforts have focused on the development of smart bandages that can perform multiple functions. In this direction, here, we designed a low cost (U$0.012 per cm2) multifunctional therapeutic wound dressing fabricated by loading curcumin (CC) into poly(ϵ-caprolactone) (PCL) nanofibers using solution blow spinning (SBS). The freestanding PCL/CC bandages were characterized by distinct physicochemical approaches and were successful in performing varied functions, including controlled release of CC, colorimetric indication of the wound conditions, barrier against microorganisms, being biocompatible, and providing a photosensitive platform for antimicrobial photodynamic therapy (aPDT). The chemical nature of PCL and CC and the interactions between these components allowed CC to be released for 192 h (ca. 8 days), which could be correlated with the Korsmeyer-Peppas model, with a burst release suitable to treat the inflammatory phase. Due to the CC keto-enol tautomerism, an optical indication of the healing status could be obtained using PCL/CC, which occurred immediately, ranging between red/orange and yellow shades. The effect against pathogenic microorganisms evaluated by agar disc-diffusion, affected skin wound simulation (ex vivo), and microbial penetration tests demonstrated the ability to block and inhibit microbial permeation in different environments. The biocompatibilities of PCL and PCL/CC were verified by in vitro cytotoxicity study, which demonstrated that cell viabilities average above 94 and 96% for human dermal fibroblasts. In addition, the proposed bandage responded to aPDT applied to an in vivo assay, showing that, when irritated, PCL/CC was able to reduce the bacteria present on the real wound of mice. In summary, our findings demonstrate that using PCL and CC to produce nonwovens by the SBS technique offers potential for the rapid fabrication of biocompatible and multifunctional wound dressings, paving the way for large-scale production and utilization of such dressings in the treatment of skin wounds.

Effect of different disinfection protocols in bacterial viability of an intraradicular biofilm formed in situ.

The present study aimed to evaluate bacterial viability after the use of different disinfection protocols in root canals infected with a multispecies biofilm (MB) formed in situ. Palatal roots with a single canal were obtained from extracted maxillary molars and sterilized before being inserted into the mouth. The roots were contaminated with a MB in an intraoral appliance worn by ten volunteers. All volunteers wore six roots simultaneously in two intraoral devices for 21 days. One root from each volunteer was assigned to each group (n=10): PUI - passive ultrasonic irrigation; EC - Easy Clean; XPF - XP-endo Finisher; aPDT - antimicrobial photodynamic therapy; CI - conventional irrigation; and NC - negative control. The samples were evaluated under confocal laser scanning microscopy. The percentage of viable cells (VC) was calculated over the total percentage of MB biovolume. Data were statistically analyzed (α=5%). The cell viability in the entire root canal or for each third was compared between groups (Kruskal-Wallis test, Dunn post-hoc test) and for the same group (Friedman test, Dunn post-hoc test). Disinfection protocols were not significantly different from each other (P>.05). Samples in EC, PUI, and aPDT had lower cell viability than in NC (P<.05). In the coronal third of samples in the EC, XPF, PUI and aPDT, the percentage of VC biovolume was lower than in the NC (P<.05). The percentage of VC in EC samples was lower in the coronal and middle thirds than in the apical third (P<.05). EC, PUI and aPDT had significant effects on cell viability in intraradicular multispecies biofilm formed in situ when compared with untreated samples.

EPS9.08 Antimicrobial photodynamic therapy with Ru(II)-loaded polymer nanocarriers towards treatment of bacterial lung infections: Proof-of-concept using cystic fibrosis Pseudomonas aeruginosa isolates

Objectives: Cystic fibrosis (CF) patients suffer from severe chronic lung infections that are caused mainly by Pseudomonas aeruginosa. As this highly adaptable pathogen is increasingly resistant to antibiotics, the development of new antimicrobial treatments is of major interest. Antimicrobial photodynamic therapy (aPDT) combines the use of photosensitizers (PS) and light to locally generate reactive oxygen species, including singlet oxygen (1O2), at the infection site. In this work, ruthenium (II) PS complexes were incorporated into polymeric micelles and vesicles to overcome the limited solubility and stability of the neat complexes, and to facilitate their delivery through the highly viscous airway mucus. Further, on-demand bacterial enzyme-triggered release of PS should minimize lung tissue damage, while maximizing local bacterial killing efficiency.

Investigation of antibacterial photodynamic inactivation in urea-doped TiO2 sensitized with porphyrin photocatalysis

Choosing the right photosensitizers (PSs) as well as the right light source is very critical in antimicrobial photodynamic therapy (aPDT). Some light sources, such as ultraviolet, have high cytotoxicity and poor penetration and some PSs are hydrophobic with low solubility in water, and easy aggregation. To address these issues, we modified TiO2 nanoparticles with urea and TCPP (TCPP=tetra(4-carboxyphenyl) porphyrin) as a PS and prepared N-doped-TiO2 (NT), TCPP/TiO2 (PT), and TCPP/N-doped-TiO2 (PNT). Urea is a safe compound used here as a source of nitrogen (N). Nitrogen doping produces a localized N state within the TiO2 bandgap which broadens the absorption in the visible light region. Both urea and TCPP shifted the bandgap of TiO2 to the visible area and enabled the photodegradation of methylene blue after 30 min of aging under visible light. 1O2 production was monitored by the rapid and irreversible conversion of anthracene to its corresponding endoperoxide. Meanwhile, different scavengers such as p-benzoquinone (p-BQ) and tert-butanol (t-BuOH) were employed in a photocatalytic process to specify the existence of superoxide and hydroxyl radical species, respectively. PNT showed a promising photobactericidal activity and reached 100% of inhibition activity against both types of bacteria after 120 and 180 min, respectively under LED lamp (15 W) irradiation. The interaction between PNT and bacteria was also examined by FESEM.

Strengthening collaborations at the Biology-Physics interface: trends in antimicrobial photodynamic therapy.

The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and effective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT field involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an effective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat different infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers.

Galleria mellonella-A Model for the Study of aPDT-Prospects and Drawbacks.

Galleria mellonella is a promising in vivo model insect used for microbiological, medical, and pharmacological research. It provides a platform for testing the biocompatibility of various compounds and the kinetics of survival after an infection followed by subsequent treatment, and for the evaluation of various parameters during treatment, including the host-pathogen interaction. There are some similarities in the development of pathologies with mammals. However, a limitation is the lack of adaptive immune response. Antimicrobial photodynamic therapy (aPDT) is an alternative approach for combating microbial infections, including biofilm-associated ones. aPDT is effective against Gram-positive and Gram-negative bacteria, viruses, fungi, and parasites, regardless of whether they are resistant to conventional treatment. The main idea of this comprehensive review was to collect information on the use of G. mellonella in aPDT. It provides a collection of references published in the last 10 years from this area of research, complemented by some practical experiences of the authors of this review. Additionally, the review summarizes in brief information on the G. mellonella model, its advantages and methods used in the processing of material from these larvae, as well as basic knowledge of the principles of aPDT.

Vancomycin-Loaded Porphyrinic MOF Nanoparticles for Killing Pathogenic Bacteria

The synthesis of functional antibacterial nanoplatforms for killing pathogenic bacteria is urgent. Among them, combining traditional antibiotics with antimicrobial photodynamic therapy (PDT) is an attractive means. Here, we synthesized a multimodal antibacterial nanoplatform (denoted as Van/PCN) based on PCN-224 and vancomycin (Van). PCN-224 is a kind of photosensitizer-based nanoscale metal organic framework (pMOF), which not only possessed large surface area and many binding sites for loading Van but also had the ability to produce ROS under visible light irradiation. Van/PCN killed bacteria by Van and ROS, achieving a synergistic antibacterial effect. Since Gram-positive bacteria are sensitive to Van, this antibacterial nanoplatform has great potential to treat bacterial infections caused by Gram-positive pathogens.

Enhancing antimicrobial photodynamic therapy with phenothiazinium dyes and sodium dodecyl sulfate against Candida albicans at various growth stages

BackgroundThe eradication of C. albicans is difficult due to the organization of the yeast in biofilms. Photodynamic therapy (PDT) has been proposed as an alternative to antifungals. Phenothiazinium dyes, e.g. methylene blue (MB), have been proposed as photosensitizing agents (PS), and their association with sodium dodecyl sulfate (SDS) has recently been shown to improve the effectiveness of PDT in planktonic culture. In this sense, the objective of this work was to evaluate the effect of PDT with phenothiazinium dyes associated to SDS in biofilms at the different stages of growth. MethodsExperiments were carried out to evaluate the effects of PDT on biofilm formation and on established biofilms of C. albicans ATCC 10231. Samples were exposed to PS 50 mg/L (MB, Azure A – AA, Azure B - AB and dimethyl methylene blue - DMMB) dissolved in water or 0.25% SDS, for 5 min in the dark. After irradiation at 660 nm, 37.3mW/cm2 for 27 min, 60.4J/cm2 colony forming units count assay (CFU/mL) was performed. One or two irradiations were applied. Statistical methods were used to assess effectiveness. ResultsPSs showed low toxicity in the dark. An application of PDT irradiation was not able to reduce the CFU/mL both in mature biofilms (24h) and in biofilms in the dispersion phase (48h), only in the adherence phase did PDT prevent the formation of biofilms. With two successive applications of PDT irradiation in the dispersion phase, PDT with MB, AA, and DMMB completely inactivated C. albicans. The similar was not observed with mature biofilms. ConclusionsDifferent stages of biofilm growth respond differently to PDT, with the greatest inhibitory effect found in the adhesion stage. Mature and dispersed biofilms are less susceptible to PDT. The use of two successive applications of PDT with PSs associated with SDS may be a useful approach to inactivate C. albicans biofilms.

Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

Bacterial biofilms pose severe threats to public health worldwide and are intractable by conventional antibiotic treatment. Antimicrobial photodynamic therapy (PDT) is emerging as a promising strategy for eradicating biofilms by virtue of low invasiveness, broad-spectrum antibacterial activity, and nondrug resistance. However, its practical efficacy is impeded by the low water solubility, severe aggregation, and poor penetration of photosensitizers (PSs) into the dense extracellular polymeric substances (EPS) of biofilms. Herein, we develop a dissolving microneedle (DMN) patch composed of a sulfobutylether-β-cyclodextrin (SCD)/tetra(4-pyridyl)-porphine (TPyP) supramolecular PS for enhanced biofilm penetration and eradication. The inclusion of TPyP into the SCD cavity can drastically inhibit the aggregation of TPyP, thereby allowing for nearly tenfold reactive oxygen species production and high photodynamic antibacterial efficacy. Moreover, the TPyP/SCD-based DMN (TSMN) possesses excellent mechanical performance that can easily pierce the EPS of biofilm with a penetration depth of ∼350 μm, enabling sufficient contact of TPyP with bacteria and optimal photodynamic elimination of bacterial biofilms. Furthermore, TSMN could efficiently eradicate Staphylococcus aureus biofilm infection in vivo with good biosafety. This study offers a promising platform for supramolecular DMN for efficient biofilm elimination and other PDTs.

Photodynamic and photothermal therapies for bacterial infection treatment

AbstractBacteria can cause numerous infectious diseases and has been a major threat to human humans. Although antibiotics have partially succeeded in treating bacteria, owing to antibiotic abuse, the emergence of multidrug‐resistant (MDR) bacteria has drastically diminished their potency. Since the invention of laser, the combination of light and photosensitizers, photodynamic therapy (PDT), has become an effective noninvasive treatment along with photothermal therapy (PTT), in which heat is generated by nonradiative relaxation. Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection, particularly against MDR bacteria. This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

Efficacy of methylene blue and curcumin mediated antimicrobial photodynamic therapy in the treatment of indirect pulp capping in permanent molar teeth

PurposeThis study aimed to evaluate the adhesive bond strength and antibacterial efficacy of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) and curcumin (CUR)-mediated aPDT versus the conventional disinfectants, such as chlorhexidine gluconate (CHX) gel and sodium hypochlorite (NaOCl), for indirect pulp capping (IPC) treatment of permanent molars. MethodsOne Hundred grossly carious human permanent molars were collected through non-traumatic extraction. All specimens were embedded in polyvinyl cross-sections to the cemento-enamel junction. The cavity preparation was conducted by grinding the samples using silicon carbide discs. After culturing Streptococcus mutans (S. mutans), a 10 µL of S. mutans suspension (106 colony forming units/mL) was transferred in each tooth cavity and anaerobically incubated for 48 h at 37 °C. All specimens were randomly divided into 5 groups: Group-I: samples treated IPC; Group-II: samples treated with 2% CHX gel; Group-III: samples treated with 6% NaOCl; Group-IV: irradiation of prepared cavity with MB-mediated aPDT; and Group-V: irradiation of prepared cavity with CUR-mediated aPDT. After disinfection methods, the universal adhesive was used, and all specimens were restored using giomer. Eventually, confocal laser scanning microscopy, shear bond strength (SBS), micro-tensile bond strength (μTBS), four-point bending strength (4P-BS) analyses were performed, and the data were analyzed statistically. ResultsAt baseline, the highest SBS (48.8 ± 6.5 MPa), μTBS (54.3 ± 3.9 MPa), and 4P-BS (123 ± 32 MPa) scores were demonstrated by the samples treated with MB-mediated aPDT. However, after 12 months of storage, the highest SBS (42.3 ± 3.9 MPa) and μTBS (45.2 ± 6.6 MPa) scores were shown by samples treated with MB-mediated aPDT, while CUR-mediated aPDT treated samples demonstrated the highest 4P-BS scores (70 ± 18 MPa). Moreover, the highest antibacterial activity against S. mutans was shown by the samples treated with MB-mediated aPDT. ConclusionsThe application of aPDT, especially MB-mediated, demonstrated superior SBS, μTBS, and 4P-BS values as well as antibacterial activity against S. mutans as compared to 2% CHX gel and 6% NaOCl as cavity disinfectants for IPC treatment of permanent molars.

Clinical and bacterial periodontal parameters with methylene blue-loaded nanoparticles incorporated in a natural plant-based vehicle for the treatment of Stage III Grade B periodontitis.

AimThe aim of the present clinical trial was to assess the effectiveness of antimicrobial photodynamic therapy (PDT) versus poly-L-glycolic acid nanoparticles loaded methylene blue in aloe vera gel (PGA/MB/AV) on periodontal and microbial outcomes in patients with Stage III Grade B periodontitis. MethodsSeven-five patients undergoing scaling and root planing (SRP) were randomized equally into three groups: Group-I: PGA/MB/AV + SRP, Group-II: PDT + SRP, and Group-III: SRP alone. The assessed clinical periodontal parameters included plaque scores (PS), bleeding on probing (BOP), pocket depth (PD), and clinical attachment levels (CAL). Plaque samples were acquired from the patients to assess the levels of Tannerella forsythia (Tf) and Porphyromonas gingivalis (Pg). Clinical and bacterial recording were documented at the start of the study, 3 months, and 6 months after completion of treatment. ResultsA significant improvement was observed in both PS and BOP at the 3 months (p<0.01) and 6 months (p<0.001) follow-up in all three groups. A significant reduction in BOP scores was observed in Group II in comparison to the other groups on the inter-group comparison. Group-I showed significant PD reduction and CAL gain compared to Group II and III (p<0.01). Group-I displayed a significant decrease in the Tf and Pg after 3 months (p<0.05). A decrease was observed after six months of treatment for Tf only (p<0.05). Group I displayed a high decrease for only Tf at three months (p<0.05). ConclusionMethylene blue-loaded nanocarrier in AV gel produced pronounced periodontal healing compared to aPDT alone in stage III grade B periodontitis patients.

Ultrasonic irradiation enhanced the efficacy of antimicrobial photodynamic therapy against methicillin-resistant Staphylococcus aureus biofilm

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 μM. 532 nm laser (40 mW/cm2, 10 min) and 1 MHz ultrasound (500 mW/cm2, 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA.

Antimicrobial Photodynamic Therapy against Escherichia coli and Staphylococcus aureus Using Nanoemulsion-Encapsulated Zinc Phthalocyanine.

Multidrug-resistant microorganisms have become a significant public health threat, and traditional antibiotics are becoming ineffective. Photodynamic therapy (PDT) is a promising alternative that utilizes photosensitizers and light to produce Reactive Oxygen Species (ROS) that can kill microorganisms. Zinc phthalocyanine (ZnPc) is a promising photosensitizer due to its strong affinity for encapsulation in nanoemulsions and its antimicrobial properties. In this study, nanoemulsion was prepared using Miglyol 812N, a surfactant, and distilled water to dissolve hydrophobic drugs such as ZnPc. The nanoemulsion was characterized by its particle size, polydispersity index, Transmission Electron Microscope and Zeta potential, and the results showed that it was an efficient nanocarrier system that facilitated the solubilization of hydrophobic drugs in water. The use of ZnPc encapsulated in the nanoemulsion produced through the spontaneous emulsification method resulted in a significant reduction in cell survival percentages of gram-positive Staphylococcus aureus and gram-negative Escherichia coli by 85% and 75%, respectively. This may be attributed to the more complex cell membrane structure of E. coli compared to S. aureus. This demonstrates the potential of nanoemulsion-based PDT as an effective alternative to traditional antibiotics for treating multidrug-resistant microorganisms.

Anticandidal Efficacy of Erythrosine with Nano-TiO2 and Blue LED-Mediated Photodynamic Therapy against Candida albicans Biofilms on Acrylic Resin: A Preliminary Study.

Incorporating an enhancer such as nano-titanium dioxide into antimicrobial photodynamic therapy can improve treatment outcome.This study aimed to compare the anticandidal efficacy of photodynamic therapy by erythrosine with nano-titanium dioxide (nano-TiO2) stimulated by a blue light emitting diode with three standard dental antifungal agents. Candida albicans biofilms on acrylic resin plates were treated for 15 minutes with either nystatin, fluconazole, Polident, 220µM erythrosine + 1% (w/w) nano-TiO2 + 15 J/cm2 blue light photodynamic therapy (Ery PDT), or distilled water. For the Ery PDT group, blue light was applied for 1 minute after incubation. After 1, 3, and 6 hours, the colony forming units in log10 (log10CFU/mL) were compared. The ultrastructure of C. albicans on the acrylic resin plates treated with erythrosine + nano-TiO2 + blue light was examined using transmission electron microscopy at magnification of 30,000x. After 1 hour, nystatin, Polident, and Ery PDT indifferently inhibited C. albicans. At 6 hours, Ery PDT reduced the number of viable C. albicans in biofilms by 0.28log10 CFU/mL, which was equal to the effect of fluconazole and Polident. Transmission electron microscopy demonstrated that Ery PDT altered the C. albicans cell morphology by inducing cell wall/membrane rupture. Photodynamic therapy with erythrosine + nano-TiO2 + blue light at low light power density (15 J/cm2) was as effective at inhibiting C. albicans biofilm on acrylic resin as fluconazole and Polident.

The combination of methylene blue and sodium dodecyl sulfate enhances the antimicrobial photodynamic therapy of Candida albicans at lower light parameters

BackgroundThe growth of resistant microorganisms has been a challenge for health systems. Antimicrobial Photodynamic Therapy (aPDT) has gained attention due to its effects on resistant strains. Recently, it was shown that the association of methylene blue (MB) and sodium dodecyl sulfate (SDS) are an effective strategy to increase the effect of aPDT; however, it is unknown which are the best light parameters (such as irradiance and radiant exposure, RE), to reach the most effective protocols. This work aimed to evaluate the light parameters, irradiance, and radiant exposure, in aPDT with MB when conveyed in water compared to MB associated with SDS. MethodsTests were carried out to quantify the colony-forming units (CFU) of ATCC 10,231 strain of Candida albicans when using MB in different media and with different light parameters: Control (water), SDS (0.25%), MB (20 mg/mL), and the MB/SDS at irradiances of 3.7; 11.2; 18.6, and 26.1 mW/cm2 and varied irradiation times to reach radiant exposures of 4.4; 17.8; 26.7, and 44 J/cm². ResultsThe results showed that aPDT with MB/SDS had a higher antimicrobial effect than MB when conveyed in water. Furthermore, for the highest irradiance studied (26.1 mW/cm2), CFU decreases exponentially with increasing RE from 4.4 up to 44 J/cm2. Similarly, at a fixed RE, the higher the irradiance used, the higher the antimicrobial effect was observed, except for the lowest RE studied (4.4 J/cm2). ConclusionsaPDT with MB/SDS had a greater antimicrobial action at the lower light parameters when compared to MB conveyed in water. The authors suggest the use of RE above 18 J/cm2 and irradiance above 26 mW/cm2 since at the mentioned parameters the increase in its value caused a greater antimicrobial effect.

Photo-responsive polymeric micelles for the light-triggered release of curcumin targeting antimicrobial activity.

Nanocarriers have been successfully used to solubilize, deliver, and increase the bioavailability of curcumin (CUR), but slow CUR release rates hinder its use as a topical photosensitizer in antimicrobial photodynamic therapy. A photo-responsive polymer (PRP) was designed for the light-triggered release of CUR with an effective light activation-dependent antimicrobial response. The characterization of the PRP was compared with non-responsive micelles comprising Pluronics™ P123 and F127. According to the findings, the PRP formed photo-responsive micelles in the nanometric scale (< 100 nm) with a lower critical micelle concentration (3.74 × 10-4 M-1, 5.8 × 10-4 M-1, and 7.2 × 10-6 M-1 for PRP, F127, P123, respectively, at 25°C) and higher entrapment efficiency of CUR (88.7, 77.2, and 72.3% for PRP, F127, and P123 micelles, respectively) than the pluronics evaluated. The PRP provided enhanced protection of CUR compared to P123 micelles, as demonstrated in fluorescence quenching studies. The light-triggered release of CUR from PRP occurred with UV light irradiation (at 355 nm and 25 mW cm-2) and a cumulative release of 88.34% of CUR within 1 h compared to 80% from pluronics after 36 h. In vitro studies showed that CUR-loaded PRP was non-toxic to mammal cell, showed inactivation of the pathogenic microorganisms Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus, and decreased biofilm biomass when associated with blue light (455 nm, 33.84 J/cm2). The findings show that the CUR-loaded PRP micelle is a viable option for antimicrobial activity.

Combination of Two Photosensitisers in Anticancer, Antimicrobial and Upconversion Photodynamic Therapy.

Photodynamic therapy (PDT) is a special form of phototherapy in which oxygen is needed, in addition to light and a drug called a photosensitiser (PS), to create cytotoxic species that can destroy cancer cells and various pathogens. PDT is often used in combination with other antitumor and antimicrobial therapies to sensitise cells to other agents, minimise the risk of resistance and improve overall outcomes. Furthermore, the aim of combining two photosensitising agents in PDT is to overcome the shortcomings of the monotherapeutic approach and the limitations of individual agents, as well as to achieve synergistic or additive effects, which allows the administration of PSs in lower concentrations, consequently reducing dark toxicity and preventing skin photosensitivity. The most common strategies in anticancer PDT use two PSs to combine the targeting of different organelles and cell-death mechanisms and, in addition to cancer cells, simultaneously target tumour vasculature and induce immune responses. The use of PDT with upconversion nanoparticles is a promising approach to the treatment of deep tissues and the goal of using two PSs is to improve drug loading and singlet oxygen production. In antimicrobial PDT, two PSs are often combined to generate various reactive oxygen species through both Type I and Type II processes.

Evaluation of photodynamic therapy on nanoparticles and films loaded-nanoparticles based on chitosan/alginate for curcumin delivery in oral biofilms

Nanoparticles and nanoparticle-loaded films based on chitosan/sodium alginate with curcumin (CUR) are promising strategies to improve the efficacy of antimicrobial photodynamic therapy (aPDT) for the treatment of oral biofilms. This work aimed to develop and evaluate the nanoparticles based on chitosan and sodium alginate encapsulated with CUR dispersed in polymeric films associated with aPDT in oral biofilms. The NPs were obtained by polyelectrolytic complexation, and the films were prepared by solvent evaporation. The photodynamic effect was evaluated by counting Colony Forming Units (CFU/mL). Both systems showed adequate characterization parameters for CUR release. Nanoparticles controlled the release of CUR for a longer period than the nanoparticle-loaded films in simulated saliva media. Control and CUR-loaded nanoparticles showed a significant reduction of 3 log10 CFU/mL against S. mutans biofilms, compared to treatment without light. However, biofilms of S. mutans showed no photoinactivation effect using films loaded with nanoparticles even in the presence of light. These results demonstrate the potential of chitosan/sodium alginate nanoparticles associated with aPDT as carriers for the oral delivery of CUR, offering new possibilities to improve the treatment of dental caries and infections. This work will contribute to advances in the search for innovative delivery systems in dentistry.