Article

Curcumin as a photosensitizer: From molecular structure to recent advances in antimicrobial photodynamic therapy

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Nowadays multi-drug resistant microorganisms is a serious public health problem worldwide. To overcome it, new antimicrobial strategies have been developed. Among them, antimicrobial photodynamic therapy is an efficient tool against various micro-organisms in different medical and healthcare fields. The antimicrobial photodynamic protocol is based on the interaction of a photosensitizer, molecular oxygen, and an appropriate light source. Herein, we described the main physical and chemical proprieties of curcumin, an useful natural photosensitizer, including its degradation pathways, analytical methods for quantification, extraction method, synthetic methodologies, and pharmaceutical formulations used. Moreover, a comprehensive review of the past 10 years (2010−2019) concerning the application of curcumin as photosensitizer against microorganisms is described and discussed.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... So, using APDT several times does not produce any resistant strains. The reasons behind this are firstly the treatment (photosensitizer + light) time is very short to develop any resistance (18,19). Next, photosensitizers do not have any dark toxicity effect and sometimes microorganisms cannot sense or understand the ROS mechanisms for their death. ...
... Third, the cells are too damaged after PDT, disabling them to confer cross-generation adaptively. Lastly, APDT does not target a single site in bacteria, much different from conventional antibiotics (18)(19)(20). ...
... Numerous in vivo and APDT tests were directed with animal model to treat different infections including skin and wounds, endodontic infections, burns, oral diseases, osteomyelitis, gastrointestinal, tuberculosis, and diverse fungal diseases (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). ...
Article
Antimicrobial photodynamic therapy (APDT), a novel tool for combating the drug resistant microorganisms which is combined with modern technologies and tools. The versatile and wide range of available photosensitizers (PS) and different wavelength light combinations opened so many ways to kill potential disease-causing pathogens. The research is developing so fast with the help of photochemistry, photobiology and photophysics. This is the beginning of new era of another antimicrobial solutions compared to conventional antibiotics. Many articles have published regarding studies on APDT and its applications. This method has shown successful eliminations of pathogenic microorganisms in skin, dental and foot infections as well as tumor or cancer treatment. The findings shared the knowledge of safe and resistance free alternative treatment of antibiotics which has clinical importance globally. This review highlights the concept, history, mechanisms, applications and the advantages of APDT. Stamford Journal of Microbiology, 2023. Vol. 13, Issue 1, p. 30-37
... The results obtained were compared with those obtained for CUR and are reported in Table 2. In agreement with data reported by other authors [37,38], CUR has a high stability to irradiation with white light. Despite the fact that HCurc I and HCurc II were significantly less stable than CUR, showing complete molecule degradation in 30 min, their Ru(II)-arene derivatives (1-6) demonstrated higher stability, comparable to that of CUR. ...
... Among natural antimicrobial photosensitizers, CUR was mostly investigated in Gram-positive strains such as Streptococcus mutans, Staphylococcus aureus (methicillin-sensitive and resistant strains), and Enterococcus faecalis. Among Gram-negative bacteria, few studies were performed on Escherichia coli and Pseudomonas aeruginosa [37]. Studies about the toxicity of CUR and CUR derivatives were already performed on alternative models, such as G. mellonella, showing no toxicity in vivo in these animal models [63][64][65]. ...
... Among natural antimicrobial photosensitizers, CUR was mostly investigated in Gram-positive strains such as Streptococcus mutans, Staphylococcus aureus (methicillin-sensitive and resistant strains), and Enterococcus faecalis. Among Gram-negative bacteria, few studies were performed on Escherichia coli and Pseudomonas aeruginosa [37]. ...
Article
Full-text available
Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical–physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.
... Recently, one of the strategies adopted by the food industry to remove microorganisms from fruits is the antimicrobial photodynamic therapy (aPDT); this technique requires the use of a light source with a specific wavelength and a photosensitizer compound to produce reactive oxygen species (ROS), which are cytotoxic and kill microorganisms when in contact with them. aPDT is most widely used for medical applications, such as infections and cancer [11][12][13], but many studies have been focusing on the development and improvement of this technique for food decontamination [14][15][16]. Most of these studies use curcumin as a photosensitizer compound capable of activating the photoinactivation process; however, other vegetable extracts rich in phenolic compounds, like the pomegranate peel one, can be explored regarding their photosensitizer potential, opening new perspectives for the use of phenolics-rich extracts from agro-industrial waste [17]. ...
... To evaluate the (photo)antimicrobial activity of the films under light application, the aPDT test was performed against S. aureus (ATCC 25923), according to the procedure described by Dias & Bagnato [12]. For that, 1 mL of the standardized bacteria suspension (0.84 mg L -1 ) were applied as negative (NC) and positive controls (PC), respectively [13]. were collectively cultivated in a 50 L aquarium (50 × 25 × 40 cm), coupled to a filtration and continuous aeration system. ...
... Moreover, PC showed a significantly smaller root elongation value, demonstrating that the TRF herbicide had phytotoxicity action for the tested organism A. cepa. 13 diameter CS/PMAA nanoparticles, no significant changes were observed in the mitotic index at the concentrations evaluated, indicating that it had no potential cytotoxicity [36]. ...
... However, it has been reported that when curcumin was applied to food sterilization, its poor water solubility and stability limited its application (Dias et al., 2020). In the past reports, the application of curcumin in food antibacterial field involved the use of organic solvents, which has some safety risks (Dias et al., 2020). ...
... However, it has been reported that when curcumin was applied to food sterilization, its poor water solubility and stability limited its application (Dias et al., 2020). In the past reports, the application of curcumin in food antibacterial field involved the use of organic solvents, which has some safety risks (Dias et al., 2020). For lipophilic compounds like curcumin, many encapsulation systems at the nanoscale had been investigated to overcome the limitations (Silva et al., 2020), such as nanoemulsion (Sepahvand et al., 2021;Xu et al., 2020), cyclodextrins (Abarca et al., 2016;Martínez-Hernández et al., 2019), zein nanoencapsulation (Suwannasang et al., 2021;Wang et al., 2016), and lipid-based nanosystems (Fathi et al., 2013;Radi et al., 2022). ...
... After 30 min of illumination, the PDI treatment with 100 µM free curcumin (L + C +) decreased the cell count of E. coli and S. aureus to 6.26 log 10 CFU/ mL and 6.63 log 10 CFU/mL, respectively. The low solubility of curcumin in saline solution might have contributed to this result (Dias et al., 2020), resulting in low efficiency of photodynamic inactivation. Moreover, the cell counts of E. coli in PDI treatment with 100 µM CS (L + CS +) decreased to 3.90 log 10 CFU/mL, while no survival S. aureus was observed (data not shown). ...
Article
Full-text available
Curcumin solid lipid nanoparticles were prepared by microemulsion method, and the physicochemical properties of these products were characterized. High encapsulation efficiency and good stability were presented (encapsulation efficiency: 89.86%, drug load rate: 28.63%, particle size: 291 ± 5.34 nm, zeta potential: − 44.4 ± 0.46 mV, stability time: > 4 weeks). The antibacterial experiments through photodynamic inactivation against two food-related microorganisms were carried out in carrot juice. The results demonstrated that the inactivation efficiency of photodynamic inactivation mediated by curcumin solid lipid nanoparticles was greater than that of free curcumin, and more stable in preserved quality at that. Moreover, the microbiota in photodynamic inactivation mediated by curcumin solid lipid nanoparticles group was kept below limit of detection for 28 days of storage while viable microorganisms were detected in free curcumin group. This study identified that photodynamic inactivation mediated by curcumin solid lipid nanoparticles could meet the requirements of food sterilization and produce safe carrot juice with preserved quality attributes.
... Curcumin (8), a naturally occurring molecule extracted from the roots of Curcuma longa L. (turmeric), in addition to medicinal properties, has shown great potential as a PS for aPDT [85]. shows potent and broad-spectrum antimicrobial activity, even against fish such as S. marcescens and P. putida [64]. ...
... Curcumin (8), a naturally occurring molecule extracted from the roots longa L. (turmeric), in addition to medicinal properties, has shown great pote for aPDT [85]. ...
Article
Full-text available
Increased infectious diseases and the reduced effectiveness of antibiotics due to antimicrobial resistance pose global challenges affecting the aquaculture industry. As bacteria increasingly develop antibiotic resistance, research scientists are shifting their focus to technologies such as antimicrobial photodynamic therapy (aPDT), which show potential for treating and controlling fish infections without promoting the development of resistant bacteria. Various photosensitizers (PSs), both natural and synthetic, are under investigation for their application in aPDT within the aquaculture industry. This shift is crucial for the sustainability of the aquaculture industry, which plays a significant role in achieving several of the United Nations (UN) Sustainable Development Goals (SDGs). This review highlights the application of aPDT against fish pathogens in the industry and the types of PSs utilized. It also explores the potential application of this technique for treating and controlling fish infections, along with the advantages and limitations of its use in aquaculture production systems. Finally, a conclusion and future perspectives are provided.
... The up-conversion method's emission range is limited to longer wavelengths by the sensitivity of the detection device; however, this limitation is not direct as the detected wavelength is shifted toward the blue end of the spectrum compared to the sample's emission range. Curcumin has outstanding chromogenic properties, allowing for robust fluorescence with visible light excitation and longer-wavelength emission [19]. The compound curcumin, which has several advantages including antibacterial, antifungal, antioxidant, and wound healing properties, is obtained by extracting the rhizome of turmeric (Curcuma longa) [20]. ...
... Rhodamin appears on the label of each cream. To calculate the energy in the cream using the results of the absorbance test in the form of wave peaks, the energy values for BC and TEC are determined as 3.63 × 10 19 Js at a peak wavelength of 547 nm and 4.89 × 10 −19 Js at a peak wavelength of 406 nm, respectively, utilizing the absorbance test. ...
Article
Full-text available
The study investigates the effect of diode laser exposure on curcumin’s skin penetration, using turmeric extraction as a light-sensitive chemical and various laser light sources. It uses an in vivo skin analysis method on Wistar strain mice. The lasers are utilized at wavelengths of 403 nm, 523 nm, 661 nm, and 979 nm. The energy densities of the lasers are 20.566 J/cm², 20.572 J/cm², 21.162 J/cm², and 21.298 J/cm², which are comparable to one another. The experimental animals were divided into three groups: base cream (BC), turmeric extract cream (TEC), and the combination laser (L), BC, and TEC treatment group. Combination light source (LS) with cream (C) was performed with 8 combinations namely 523 nm ((L1 + BC) and (L1 + TEC)), 661 nm ((L2 + BC) and (L2 + TEC)), 403 nm ((L3 + BC) and (L3 + TEC)), and 979 nm ((L4 + BC) and (L4 + TEC)). The study involved applying four laser types to cream-covered and turmeric extract–coated rat skin, with samples scored for analysis. The study found that both base cream and curcumin cream had consistent pH values of 7–8, within the skin’s range, and curcumin extract cream had lower viscosity. The results of the statistical analysis of Kruskal–Wallis showed a significant value (p < 0.05), which means that there are at least two different laser treatments. The results of the post hoc analysis with Mann–Whitney showed that there was no significant difference in the LS treatment with the addition of BC or TEC when compared to the BC or TEC treatment alone (p > 0.05), while the treatment using BC and TEC showed a significant difference (p < 0.05). Laser treatment affects the penetration of the turmeric extract cream into the rat skin tissue.
... Taking this approach with curcumin is a timely effort for aPDT applications in water matrices because it consists of a natural-based PS with low toxicity photodegradation products (Dias et al. 2020;Lima et al. 2022b). As for the additive, peroxidation is a popular decontamination practice using standalone H 2 O 2 , e.g., in the pharmaceutical industry, clinical environments, aquaculture, agriculture and poultry, food industry, and water treatment . ...
... As for aPDT as a single factor, though curcumin is known as an environmentally safe PS molecule (Dias et al. 2020;Lima et al. 2022b), it is crucial that no residuals or photoproducts are present in treated samples, particularly considering the organic input. Future work on optimal operational conditions must therefore consider mineralization of the PS. ...
Article
Full-text available
Antimicrobial photodynamic treatment (aPDT) is a photooxidative process based on the excitation of a photosensitizer (PS) in the presence of molecular oxygen, under specific wavelengths of light. It is a promising method for advanced treatment of water and wastewater, particularly targeting disinfection challenges, such as antibiotic-resistant bacteria (ARB). Research in improved aPDT has been exploring new PS materials, and additives in general. Hydrogen peroxide (H2O2) a widely applied disinfectant, mostly in the food industry and clinical settings, present environmentally negligible residuals at the usually applied concentrations, making it friendly for the water and wastewater sectors. Here, we explored the effects of preoxidation with H2O2 followed by blue light-mediated (450 nm) aPDT using curcumin (a natural-based PS) against methicillin-resistant Staphylococcus aureus (MRSA). Results of the sequential treatment pointed to a slight hampering in aPDT efficiency at very low H2O2 concentrations, followed by an increasing cooperative effect up to a deleterious point (≥7 log10 inactivation in CFU mL–1), suggesting a synergistic interaction of preoxidation and aPDT. The increased performance in H2O2-pretreated aPDT encourages studies of optimal operational conditions for the assisted technology and describes potentials for using the described strategy to tackle the issue of ARB spread.
... Many PSs are chlorophyll-and xanthene-based compounds. Additionally, many natural compounds such as curcumin [61] and hypericin are employed as PSs [62]. This natural origin explains their wide safety window. ...
Article
Full-text available
This review is concerned with chronic wounds, with an emphasis on biofilm and its complicated management process. The basics of antimicrobial photodynamic therapy (PDT) and its underlying mechanisms for microbial eradication are presented. Intrinsically active nanocarriers (polydopamine NPs, chitosan NPs, and polymeric micelles) that can further potentiate the antimicrobial photodynamic effect are discussed. This review also delves into the role of photoactive electrospun nanofibers, either in their eluting or non-eluting mode of action, in microbial eradication and accelerating the healing of wounds. Synergic strategies to augment the PDT-mediated effect of photoactive nanofibers are reviewed.
... The present study is novel as it focuses on the antibiofilm effect of erythrosin B combined with a LED light source. There are reports citing the antibiofilm effect of curcumin with LED light for medical applications, like the reduction in MRSA biofilms formed in bone cavities when treated with a 20.1 J/cm 2 dose of a blue LED (450 nm) in combination with curcumin [61,62]. The combination of curcumin and a UV lamp has been evaluated against planktonic cells relevant for food safety [57]. ...
Article
Full-text available
The development of novel antimicrobial technologies for the food industry represents an important strategy to improve food safety. Antimicrobial photodynamic disinfection (aPDD) is a method that can inactivate microbes without the use of harsh chemicals. aPDD involves the administration of a non-toxic, light-sensitive substance, known as a photosensitizer, followed by exposure to visible light at a specific wavelength. The objective of this study was to screen the antimicrobial photodynamic efficacy of 32 food-safe pigments tested as candidate photosensitizers (PSs) against pathogenic and food-spoilage bacterial suspensions as well as biofilms grown on relevant food contact surfaces. This screening evaluated the minimum bactericidal concentration (MBC), minimum biofilm eradication concentration (MBEC), and colony forming unit (CFU) reduction against Salmonella enterica, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas fragi, and Brochothrix thermosphacta. Based on multiple characteristics, including solubility and the ability to reduce the biofilms by at least 3 log10 CFU/sample, 4 out of the 32 PSs were selected for further optimization against S. enterica and MRSA, including sunset yellow, curcumin, riboflavin-5′-phosphate (R-5-P), and erythrosin B. Optimized factors included the PS concentration, irradiance, and time of light exposure. Finally, 0.1% w/v R-5-P, irradiated with a 445 nm LED at 55.5 J/cm2, yielded a “max kill” (upwards of 3 to 7 log10 CFU/sample) against S. enterica and MRSA biofilms grown on metallic food contact surfaces, proving its potential for industrial applications. Overall, the aPDD method shows substantial promise as an alternative to existing disinfection technologies used in the food processing industry.
... The results indicated that PDT effectively reduced the MIC in both tested strains compared with the isolated use of photosensitizers. This suggests that PDT is a promising therapeutic approach for treating microbial infections, especially in cases where conventional antibiotics are limited or ineffective 5,11,14,15,18,19 . ...
Article
Full-text available
Objective: To analyze the effect of methylene blue and 10% curcumin in fungi and bacteria through an in vitro study using photodynamic therapy (PDT). Methods: Curcumin and methylene blue were photosensitized by a Photon Lase III laser applied for 90 s in a dark environment within a laminar flow chamber. Enterococcus faecalis and Candida albicans strains were cultured and standardized. Then, a minimum inhibitory concentration (MIC) assay was conducted for these photosensitizers, with concentration variations and incubation to evaluate their antimicrobial activity. Results: With PDT, Curcumin had significant antibacterial activity against E. faecalis (MIC = 250 µg/mL). In contrast, methylene blue had antibacterial activity against E. faecalis (MIC < 12.5 µg/mL with PDT) and antifungal activity against C. albicans (MIC <12.5 µg/mL with or without PDT). Both agents showed greater efficacy in the presence of the laser. The results suggest that curcumin and methylene blue associated with laser may effectively treat microbial infections. Conclusion: Further research is needed to evaluate the efficacy and safety of using these agents in animal and human models and their effectiveness against different bacterial and fungal strains.
... Curcumin(Cur) is a diketone compound extracted from the rhizomes of some Zingiberaceae and Araceae plants [5,45]. It has anti-inflammatory, antioxidant, and oxygen radical scavenging effects, which commonly applied to wound dressing. ...
Article
Polyacrylonitrile (PAN) nanofiberous membranes incorporated with different content of Curcumin (Cur), tannic acid and silver nanoparticles (AgNPs) were successfully fabricated by an electrospinning process. The analytical results from the characterizations including scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and ultraviolet-visible photometry (UV-vis) exhibited good physicochemical properties for the obtained novel electrospun composite membranes. The nanofibers exhibited smooth surface with diameter ranged between 375 and 450 nm. The AgNPs obtained by TA reduction owned an average particle diameter of 19.1 nm. There was a rapid release of AgNPs in the Cur/TA/AgNPs/PAN electrospun composite membranes within 8 h, and then a relatively stable release of AgNPs after 24 h. Sustained drug release tests on Cur revealed that the samples exhibited an initial burst response for the first 24 h, followed by sustained release for up to 192 h, which could be traced by fluorescence to observe changes of Cur. The obtained elec-trospun Cur/TA/AgNPs/PAN nanofiberous composite membrances exhibited better hydrophilicand positive antimicrobial properties. It was found that thoseelectrospun Cur/TA/AgNPs/PAN nanofiberous composite membrances could rapidly scavenge DPPH radicals within 120 s. The results from in vitro cell compatibility test that normal growth and proliferation of Bone marrow MSCs were noticed on the fiber surface within 5 days, indicating favorable biocompatibility. this novel electrospun Cur/TA/AgNPs/PAN nanofiberous composite membranes can be potentially used as the wound dressing in prevention of free radicals and bacteria to wounds.
... 29 Besides its protective properties, CUR is also known as a natural photosensitizer for antimicrobial photodynamic therapy applied against drug resistant microorganisms. 30,31 Therefore, the elementary reactions initiated by photoexcitation as well as the photochemical/photophysical processes of light absorption and energy transfer appearing in a photosensitizing agent are crucial to understanding its phototoxic effects and increasing the efficiency of the treatment. 32 The chemically induced dynamic nuclear polarization (CIDNP) method is widely used to study the molecular mechanisms of complex photochemical processes involving electron transfer and free radicals. ...
Article
Full-text available
Electron-driven processes in isolated curcumin (CUR) molecules are studied by means of dissociative electron attachment (DEA) spectroscopy under gas-phase conditions. Elementary photostimulated reactions initiated in CUR molecules under UV irradiation are studied using the chemically induced dynamic nuclear polarization method in an acetonitrile solvent. Density functional theory is applied to elucidate the energetics of fragmentation of CUR by low-energy (0–15 eV) resonance electron attachment and to characterize various CUR radical forms. The adiabatic electron affinity of CUR molecule is experimentally estimated to be about 1 eV. An extra electron attachment to the π1* LUMO and π2* molecular orbitals is responsible for the most intense DEA signals observed at thermal electron energy. The most abundant long-lived (hundreds of micro- to milliseconds) molecular negative ions CUR– are detected not only at the thermal energy of incident electrons but also at 0.6 eV, which is due to the formation of the π3* and π4* temporary negative ion states predicted to lie around 1 eV. Proton-assisted electron transfer between CUR molecules is registered under UV irradiation. The formation of both radical-anions and radical-cations of CUR is found to be more favorable in its enol form. The present findings shed some light on the elementary processes triggered in CUR by electrons and photons and, therefore, can be useful to understand the molecular mechanisms responsible for a variety of biological effects produced by CUR.
... This fact is in some cases an inconvenient problem, for example in biomedical applications such as Photodynamic Therapy (PDT) that depends on light absorption [66]. CUR has been proposed as a photosensitizer for PDT in many studies involving the control of microorganisms [67] and malignant neoplasms [68]. ...
... [14] Recently, polydopamine-curcumin nanocomposites (nPD-Cur) were successfully prepared by Lucas et al. and proved to have excellent photodynamic and photothermal effects, which were bene cial for mediating the combined antibacterial effect of Cur and nPD. [15] The PDT using nPD-Cur component accelerates drug entry into both gram-positive bacteria and gram-negative which can signi cantly enhance its antibacterial effect. In addition, this combination showed improved stability of compounds compared with Cur alone along with less cytotoxicity and hemolytic activity. ...
Preprint
Full-text available
Background: Root canal infections are a common challenge in endodontics where traditional root canal irrigants have been accompanied with photodynamic therapy(PDT) to enhance the antibacterial eradication and prevention of reinfection. This study explores a novel approach for root canal disinfection using photodynamically activated photosensitiser Curcuma longa(Cur), an active compound found in turmeric, optimized with polydopamine nanoparticles (nPD) against Enterococcus faecalis(E. faecalis) as a root canal irrigant. Methodology: Fifty three single-rooted human premolar teeth were decoronated, 2–3 mm from the cementoenamel junction was removed to obtain specimens of 10 mm length. The root canals were biomechanically prepared and the samples were rinsed in ultrasonic bath with 3% NaOCl and 17% EDTA and rinsed in distilled water. Then, specimens were autoclaved and were inoculated with 0.1mL E. faecalis in Brain Heart Infusion (BHI) broth and incubated at 37°Cfor four weeks. After E.faecalis growth, all the specimens were randomised into 5 groups (n=10); Group 1- Untreated specimens; 2. Group 2 - 2.5% NaOCl; Group 3 - PDT + Cur; Group 4 - PDT + nPD; Group 5 - PDT + nPD-Cur. Each specimen was then irrigated with respective experimental irrigation protocol followed by application of diode irradiation at wavelength of 808 nm and 405 nm simultaneously for 10 min. The samples were collected using sterile paper points immersed in root canal and cultured to determine the number of colony-forming units (CFU)/ml. Specimens were analysed under CLSM to determine the percentage of dead bacteria and SEM to evaluate biofilm disruption potential. Results: CFU, dead bacteria percentage and bioflim disruption potential revealed to be highest for NaOCl group followed by PDT+nPD > PDT+Curcumin+nPD > PDT+Curcumin. Conclusion: nPD were found to have good antibacterial properties than curcumin and nPD-Cur also proved to have enhance photodynamic antibacterial activity against endodontic biofilm.
... Another example of a natural PS with antimicrobial potential is curcumin [25]. The antimicrobial properties and use of curcumin and its derivatives are described in detail in the review [26]. The source of many endogenous antibacterial PSs is a chemically diverse group of secondary plant metabolites, alkaloids [27]. ...
... Curcumin is activated by blue light (405 to 435 nm). In addition, Cur has a range of pharmacological effects including antibacterial, anti-inflammatory, anticancer, and antitumor actions [16,17]. However, Cur is a hydrophobic material. ...
Article
Background: Periodontitis is a chronic inflammatory disease that leads to the loss of tooth-supporting structures. Porphyromonas gingivalis is one of the main pathogens responsible for periodontitis. Because of the limitations of antibiotic use, various alternative approaches have been developed. Antimicrobial photodynamic therapy uses photosensitizers and light to eliminate pathogens. Curcumin is a promising photosensitizer, but has low bioavailability and water solubility. However, dendrosomes can efficiently encapsulate curcumin, overcoming these obstacles. This study aimed to evaluate the efficacy of photodynamic therapy with blue laser and dendrosomal curcumin against Porphyromonas gingivalis. Methods: In this in vitro experiment, the minimum inhibitory concentration (MIC) of dendrosomal curcumin was determined using a serial dilution approach. Porphyromonas gingivalis suspensions were subjected to blue laser irradiation (447 nm, output power 100 mW) for 30 to 180 s. Finally, several subMIC dendrosomal curcumin concentrations and blue laser irradiation periods were applied to the bacterial suspensions. The negative control group received no therapy, whereas the positive control group was treated with 0.2% chlorhexidine. Consequently, the colony count of each group was calculated. Results: Treatment of Porphyromonas gingivalis with dendrosomal Curcumin at concentrations of 8–250 μg/mL significantly reduced bacterial growth compared to untreated group. 90 second exposure to a blue laser (31.8 J/cm2) completely inhibited the growth of Porphyromonas gingivalis. Blue laser irradiation for 60 s (21.2 J/cm2) markedly reduced bacterial growth but did not completely prevent its survival. Photodynamic therapy using dendrosomal curcumin at concentrations of 2–4 μg/mL and irradiation for 30–90 s resulted in complete eradication of Porphyromonas gingivalis compared to controls (P < 0.05). Conclusion: The reduction in survival of Porphyromonas gingivalis following photodynamic therapy with dendrosomal curcumin and blue laser indicates that this technique could be a useful approach to eradicate Porphyromonas gingivalis infections.
... Particularly in foliar pathogens, the first step in pathogenesis is the colonization of aerial tissue surfaces. Flat surfaces such as cucumber, tomato, and lettuce leaves provide excellent light exposure, and good microbial reduction was observed when the cationic curcumin derivative SACUR-3 was used against E. coli O157:H7 [38]. Bacterial pathogens can gain access to internal plant tissues either through wounds or through natural openings such as stomatal pores used for gas exchange; Fig. 2 Schematic diagram of the dry drop method. ...
Article
Full-text available
Antimicrobial resistance in agriculture is a global concern and carries huge financial consequences. Despite that, practical solutions for growers that are sustainable, low cost and environmentally friendly have been sparse. This has created opportunities for the agrochemical industry to develop pesticides with novel modes of action. Recently the use of photodynamic inactivation (PDI), classically used in cancer treatments, has been explored in agriculture as an alternative to traditional chemistries, mainly as a promising new approach for the eradication of pesticide resistant strains. However, applications in the field pose unique challenges and call for new methods of evaluation to adequately address issues specific to PDI applications in plants and challenges faced in the field. The aim of this review is to summarize in vitro, ex vivo, and in vivo/in planta experimental strategies and methods used to test and evaluate photodynamic agents as photo-responsive pesticides for applications in agriculture. The review highlights some of the strategies that have been explored to overcome challenges in the field.
... This causes a disruption in the equilibrium between prooxidants and antioxidants, shifting the balance in favor of the former and potentially causing damage. It seems that the excited states of curcumin and their subsequent chemical interactions with oxygen are responsible for mediating the phototoxicity of curcumin to fungal organisms [20,44]. ...
Article
Full-text available
The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.
Article
Full-text available
Endodontic therapy is performed by biomechanical preparation and intracanal medication; however, residual bacteria can be compromised due to their ability to adhere to the root canal walls. Therefore, photodynamic therapy has gained popularity because of its good ability to prevent and eradicate microbial infections by using a light-activated dye. Objective: Analyze and to update the information on the effect of curcumin in photodynamic therapy in root canal treatment. Material and Methods: A literature search was carried out in PubMed/MEDLINE, Scopus, Ebsco, Science Direct, and LILACS databases using the keywords "curcumin", "turmeric", "photodynamic", "photochemotherapy", "photoradiation", "photoactivated disinfection", "root canal disinfection", "root canal therapy", "endodontics" in both Spanish and English, from 2018 to 2023. Results: Information from the last five years was collected with the aim of updating the study topic. 749 articles were examined using inclusion and exclusion criteria, of which only 50 met these criteria and were analyzed. Current studies show the effects of therapy on the contamination of the root canal biofilm with E. faecalis, demonstrating that photoactivated curcumin promotes the disruption of the biofilm and reduction of Colony-Forming Units. Conclusions: Curcumin as a photosensitizer demonstrates a potential antibacterial effect significantly decreasing the viability of microbial cells and the vitality of biofilms.
Article
Full-text available
Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Curcuma longa Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin’s beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.
Article
Full-text available
Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential.
Article
Photodynamic processes have found widespread application in therapies. These processes involve photosensitizers (PSs) that, when excited by specific light wavelengths and in the presence of molecular oxygen, generate reactive oxygen species (ROS), that target cells leading to inactivation. Photodynamic action has gained notable attention in environmental applications, particularly against pathogens and antibiotic-resistant bacteria (ARB) that pose a significant challenge to public health. However, environmental matrices frequently encompass additional contaminants and interferents, including microplastics (MPs), which are pollutants of current concern. Their presence in water and effluents has been extensively documented, highlighting their impact on conventional treatment methods, but this information remains scarce in the context of photodynamic inactivation (PDI) setups. Here, we described the effects of polyvinyl chloride (PVC) microparticles in PDI targeting Staphylococcus aureus and its methicillin-resistant strain (MRSA), using curcumin as a PS under blue light. The presence of PVC microparticles does not hinder ROS formation; however, depending on its concentration, it can impact bacterial inactivation. Our results underscore that PDI remains a potent method for reducing bacterial concentrations in water and wastewater containing ARB, even in highly contaminated scenarios with MPs.
Article
Photodynamic therapy (PDT) has been widely employed in clinical applications, healthcare, and public health (e.g. cancer research, microbiological control, vector control, etc). The photodynamic action is an advanced oxidation process based on the production of reactive oxygen species (ROS) and singlet oxygen by the excitation of a photosensitizer by specific wavelengths of light in the presence of molecular oxygen. The generation of ROS, which are highly reactive, encourages the use of PDT against recalcitrant pollutants and resistant parasites, a novel approach for PDT applications. Here, we explored recent research in PDT in water and wastewater treatment, elucidating operational conditions, main targets, potentials, and constraints, considering a collection of scientific papers curated by a well-defined research strategy. Retrieved records were filtered by subjects, and data was organized into a content network. Results showed that PDT is a timely alternative to deal with emerging chemical contaminants, resistant microorganisms, and other challenges, raising opportunities for versatile applications and sustainable solutions. Advances in environmental applications of PDT may help reach the Sustainable Development Goal 6 (SDG 6), but also positively impact other SDGs.
Article
Antimicrobial photodynamic therapy (APDT) is a promising approach to overcome antimicrobial resistance. However, for widespread implementation of this approach, approved photosensitizers are needed. In this study, we used commercially available preparations ( Calendulae officinalis floridis extract, Chamomillae recutitae floridis extract, Achillea millefolii herbae extract; Hypericum perforatum extract; Eucalyptus viminalis folia extract) as photosensitizers for inactivation of gram‐negative ( Pseudomonas aeruginosa ) and gram‐positive ( Staphylococcus aureus ) bacteria. Spectral‐luminescent analysis has shown that the major chromophores are of chlorophyll (mainly chlorophyll a and b ) and hypericin nature. The extracts are efficient generators of singlet oxygen with quantum yield ( γ Δ ) from 0.40 to 0.64 (reference compound, methylene blue with γ Δ = 0.52). In APDT assays, bacteria before irradiation were incubated with extracts for 30 min. After irradiation and 24 h of incubation, colony‐forming units (CFU) were counted. Upon exposure of P. aeruginosa to radiation of 405 nm, 590 nm, and 660 nm at equal energy dose of 30 J/cm ² (irradiance – 100 mW/cm ² , exposure time – 5 min), the most pronounced effect is observed with blue light (>3 log 10 reduction); in case of S. aureus , the effect is approximately equivalent for light of indicated wavelengths and dose ( > 4 log 10 reduction).
Article
Full-text available
Three star‐like carriers with poly(hydroxy propyl methacrylate) (PHPMA) cores and poly(oligoethylene glycol methacrylate) (POEGMA) arms as nanocarriers were utilized for the encapsulation of rhodamine B, resveratrol, and curcumin. These drugs differ in hydrophobicity and therapeutic effects. The carriers had high encapsulation and loading efficiency (>95% and 10 wt%, respectively) and formed hydrogen bonds with the drugs. They were spherical in phosphate buffer saline and formed aggregates of various sizes (11–116 nm) depending on the star composition and the drug type. The carriers were stable for 2 months, but released different amounts of drugs afterwards, except for curcumin, which stayed entrapped. The curcumin‐loaded carriers also generated reactive oxygen species. These findings demonstrate the versatility of PHPMA/POEGMA stars as nanocarriers for diverse applications in nanomedicine.
Article
Full-text available
Aberrant β‐amyloid (Aβ) fibrillation is the key event in Alzheimer's disease (AD), the inhibition and degradation of which are recognized as a promising therapeutic strategy to alleviate the nerve damage of AD. Photodynamic therapy (PDT) holds great potential for modulation of Aβ self‐assembly, which is nevertheless limited by the inefficient utilization of reactive oxygen species (ROS). Herein, an erythrocyte membrane (EM)‐modified core–shell upconversion nanoparticle (UCNP/Cur@EM) is designed and fabricated as a biomimetic nanobait to improve the PDT efficiency in AD. The UCNP with the outlayer of mesoporous silica is synthesized to load a high amount of the photosensitizer (curcumin), the unique optical feature of which can trigger curcumin to generate ROS upon near‐infrared light (NIR) irradiation. Integration of EM enables the biomimetic nanobait to attract Aβ peptides trapped in the phospholipid bilayer, restraining the growth of Aβ monomers to form aggregates and improving the utilization rate of ROS to degrade the preformed Aβ aggregates. In vivo studies demonstrate that UCNP/Cur@EM irradiated by NIR enables to decrease Aβ deposits, ameliorates memory deficits, and rescues cognitive functions in the APP/PS1 transgenic mouse model. A biocompatible and controllable way is provided here to inhibit the amyloid protein‐associated pathological process of AD.
Article
Gram-negative bacteria present a significant challenge to conventional treatments due to their structurally complex cell walls, setting them apart from their gram-positive counterparts. These structural distinctions, coupled with various antimicrobial resistance mechanisms, make them highly resilient. Photodynamic inactivation (PDI) has emerged as a promising technique to address this challenge, capitalizing on oxidative stress induced by the synergy of light and a photosensitizer (PS). In this study, we delved into the application of PDI and its repercussions on both Klebsiella pneumoniae and Escherichia coli bacteria, in both pure cultures and mixed populations. Our investigation encompassed an analysis of changes in growth curves when influenced by photodynamic and the response to the susceptibility to gentamicin. Methods: Various concentrations (50 μ M, 100 μ M, and 150 μ M) of synthetic curcumin solutions served as PS in treatment groups. Additionally, solvents such as dimethyl sulfoxide and 0.1% sodium dodecyl sulfate (SDS) were evaluated to enhance PS mobility and absorption. Growth curves for pure and mixed cultures were established, both pre- and post-PDI, and in the presence of 0.1% SDS. Blue light irradiation at 30 J cm ⁻² and 450 nm was employed. The minimum inhibitory concentration (MIC) of the antibiotic was determined with and without PDI + SDS. Results: While PDI did not achieve optimal bacterial reduction for these strains, it did introduce oxidative damage that has the potential to affect other critical aspects of the temporal progression of cultures and their responses to antibiotics. Conclusion: This study shows that even with the minimal impact of PDI in the presence of 0.1% SDS, observable alterations in bacterial growth profiles and MIC values occur and can be used in favor of treatment involving such infections.
Article
Full-text available
This study provides a comprehensive overview of the current knowledge regarding phototoxic terrestrial plants and their phototoxic and photosensitizing metabolites. Within the 435,000 land plant species, only around 250 vascular plants have been documented as phototoxic or implicated in phototoxic occurrences in humans and animals. This work compiles a comprehensive catalog of these phototoxic plant species, organized alphabetically based on their taxonomic family. The dataset encompasses meticulous details including taxonomy, geographical distribution, vernacular names, and information on the nature and structure of their phototoxic and photosensitizing molecule(s). Subsequently, this study undertook an in‐depth investigation into phototoxic molecules, resulting in the compilation of a comprehensive and up‐to‐date list of phytochemicals exhibiting phototoxic or photosensitizing activity synthesized by terrestrial plants. For each identified molecule, an extensive review was conducted, encompassing discussions on its phototoxic activity, chemical family, occurrence in plant families or species, distribution within different plant tissues and organs, as well as the biogeographical locations of the producer species worldwide. The analysis also includes a thorough discussion on the potential use of these molecules for the development of new photosensitizers that could be used in topical or injectable formulations for antimicrobial and anticancer phototherapy as well as manufacturing of photoactive devices.
Article
The development of biodegradable and biocompatible fluorescent materials with tunable emission in the solid state has become increasingly relevant for smart packaging and biomedical applications. Molecular packing and conformations play a critical role in tuning the solid-state photophysical properties of fluorescent materials. In this work, tunable emission of bioactive curcumin was achieved through the manipulation of the crystallization conditions and the polymorphic form of covalently linked poly(L-lactide) in the curcumin-embedded poly(L-lactide) (curcumin-PLLA). In the melt-crystallized curcumin-PLLA, with the increase in the isothermal crystallization temperature, a bathochromic shift in the fluorescence of curcumin-PLLA was observed due to the change in the intramolecular conjugation length of curcumin. The change in the isothermal crystallization temperature of curcumin-PLLA resulted in the rotation of the terminal phenyl rings of curcumin with respect to the central keto-enol group due to the covalently linked helical PLLA chains. In addition, solvent-induced single crystals and a gel of curcumin-PLLA were prepared and the influence of the polymorphic form of PLLA on the emission behavior of curcumin-PLLA was investigated. The results suggest that the polymer chain packing, crystallization conditions, morphology, and polymorphic form could play an influential role in dictating the fluorescence properties of fluorophore-embedded polymers.
Article
The misuse of antibiotics leading to bacterial multidrug resistance is responsible for severe infectious diseases and a significant cause of mortality worldwide, resulting in numerous human disasters. Photodynamic antibacterial therapy (PDAT) is a promising strategy against multiantibiotic-resistant bacteria, but its antibacterial activity is greatly limited by reduced glutathione (GSH) in bacteria. In this study, we constructed a nanoplatform through the formation of metal chelating complexes (FeP) between ferric and pyrophosphate ions, with subsequent adsorption of the photosensitizer ZnPc(COOH)8 (octa-carboxyl substituted zinc phthalocyanine) mediated by polylysine (PL) on the surface. The nanocomplexes FeP@PL:ZnPc(COOH)8 exhibited the capacity of GSH depletion and chemodynamic activity, which synergistically enhanced PDAT efficacy. FeP@PL:ZnPc(COOH)8 possessed the excellent antibacterial activity in vivo and in vitro, which might be attributed to the increased production of reactive oxygen species (ROS), reduced GSH level in bacteria, improved bacterial uptake, and enhanced destruction of the bacterial outer membrane. Moreover, FeP@PL:ZnPc(COOH)8 exhibited accelerated wound healing efficacy and the ability to recognize bacteria-infected wounds, rendering it an effective theranostic nanoplatform for bacterial infections. The construction strategy of nanocomplexes in this study holds theoretical and practical significance for high-efficiency synergistic photodynamic and chemodynamic antibacterial therapy.
Article
Curcumin (CUR) is a naturally occurring pigment extensively studied due to its therapeutic activity and delivered by suitable nanocarriers to overcome poor solubility in aqueous media. The significant absorption of CUR in the visible blue region has prompted its use as a potential phototherapeutic agent in treating infectious and cancer diseases, although the mechanism underlying the phototoxic effects is still not fully understood. This contribution investigates the photobehaviour of CUR within polymeric micelles, microemulsions, and zein nanoparticles, chosen as biocompatible nanocarriers, and human serum albumin as a representative biomolecule. Spectroscopic studies indicate that in all host systems, the enolic tautomeric form of CUR is converted in a significant amount of the diketo form because of the perturbation of the intramolecular hydrogen bond. This leads to intermolecular H-abstraction from the host components by the lowest excited triplet state of CUR with the formation of the corresponding ketyl radical, detected by nanosecond laser flash photolysis. This radical is oxidized by molecular oxygen, likely generating peroxyl and hydroperoxyl radical species, unless in Zein, reasonably due to the poor availability of oxygen in the closely packed structure of this nanocarrier. In contrast, no detectable formation of singlet oxygen was revealed in all the systems. Overall these results highlight the key role of the H-abstraction process over singlet oxygen sensitization as a primary photochemical pathway strictly dictated by the specific features of the microenvironment, providing new insights into the photoreactivity of CUR in biocompatible hosts that can also be useful for a better understanding of its phototoxicity mechanism.
Article
Photodynamic inactivation (PDI) of microorganisms has been shown as a promising alternative against the spread of resistant bacteria. It has been used not only in clinical applications, but also in the public health sector, for water and wastewater disinfection. In order to improve efficiency, recent research has focused on novel photosensitizing materials, as well as chemical additives. To our knowledge, however, hydrogen peroxide (a widely known standalone disinfectant) has not been employed combined with curcumin (a vegetal-based and environmental-friendly photosensitizer) for PDI seeking for future environmental applications. In this sense, this study aimed to assess whether there were any competitive or cooperative effects by the simultaneous use of curcumin and hydrogen peroxide on the PDI of Staphylococcus aureus , in in-vitro batch tests. Photobleaching for individual and combined factors was performed in order to compare results of inactivation with changes in chemical aspects in solution under blue light irradiation. One may think that the combination may add strength to PDI due to hydrogen peroxide being a natural supplier of oxygen. However, antagonistic effects were found in combined treatments, implying that such combination is non profitable. The results indicate that special care is necessary when considering combining techniques.
Article
Full-text available
Consumer awareness on the side effects of chemical preservatives has increased the demand for natural preservation technologies. An efficient and sustainable alternative to current conventional preservation techniques should guarantee food safety and retain its quality with minimal side effects. Photosensitization, utilizing light and a natural photosensitizer, has been postulated as a viable and green alternative to the current conventional preservation techniques. The potential of curcumin as a natural photosensitizer is reviewed in this paper as a practical guide to develop a safe and effective decontamination tool for industrial use. The fundamentals of the photosensitization mechanism are discussed, with the main emphasis on the natural photosensitizer, curcumin, and its application to inactivate microorganisms as well as to enhance the shelf life of foods. Photosensitization has shown promising results in inactivating a wide spectrum of microorganisms with no reported microbial resistance due to its particular lethal mode of targeting nucleic acids. Curcumin as a natural photosensitizer has recently been investigated and demonstrated efficacy in decontamination and delaying spoilage. Moreover, studies have shown the beneficial impact of an appropriate encapsulation technique to enhance the cellular uptake of photosensitizers, and therefore, the phototoxicity. Further studies relating to improved delivery of natural photosensitizers with inherent poor solubility should be conducted. Also, detailed studies on various food products are warranted to better understand the impact of encapsulation on curcumin photophysical properties, photo‐driven release mechanism, and nutritional and organoleptic properties of treated foods.
Article
Full-text available
Recently varieties of Bodipy derivatives showing intersystem crossing (ISC) have been reported as triplet photosensitizers, and the application of these compounds in photocatalysis, photodynamic therapy (PDT), and photon upconversion are promising. In this review we summarized the recent development in the area of Bodipy-derived triplet photosensitizers and discussed the molecular structural factors that enhance the ISC ability. The compounds are introduced based on their ISC mechanisms, which include the heavy atom effect, exciton coupling, charge recombination (CR)-induced ISC, using a spin converter and radical enhanced ISC. Some transition metal complexes containing Bodipy chromophores are also discussed. The applications of these new triplet photosensitizers in photodynamic therapy, photocatalysis, and photon upconversion are briefly commented on. We believe the study of new triplet photosensitizers and the application of these novel materials in the abovementioned areas will be blooming.
Article
Full-text available
The increasingly limited therapeutic options for the treatment of infections caused by multi-resistant Gram-negative bacteria due to the alarming increase in bacteria resistance, renewed interest in photodynamic inactivation (PDI) of bacteria. We address PDI of multi-resistant bacteria with a new family of cationic tetra-imidazolyl phthalocyanines bearing a diversity of cationizing alkylic chain sizes, degrees of cationization and coordinating metals. The antimicrobial activities of the phthalocyanines under white light against Gram-positive and Gram-negative bacteria have remarkable differences in efficacy. We relate their spectroscopic and photophysical properties with the generation of reactive oxygen species (ROS), biological performance and structural features. We show that sub-micromolar concentrations of a Zn(II) tetra-ethyl cationic phthalocyanine reduce colonies of Gram-negative bacteria (E. coli, P. aeruginosa) and C. albicans by 7 log units while leaving mammalian cells unharmed. This is a new lead to address hard-to-treat localized infections.
Article
Full-text available
Introduction: Curcumin incorporation into polymeric fibers was tested for its antimicrobial properties and potential use in root canal disinfection. Methods: Curcumin-modified fibers were processed via electrospinning and tested against a 7-day old established Actinomyces naeslundii biofilm. The medicaments tested were as follows: curcumin-modified fibers at 2.5 and 5.0 mg/mL, curcumin-based irrigant at 2.5 and 5.0 mg/mL, saline solution (negative control), and the following positive controls: 2% chlorhexidine, 1% sodium hypochlorite, and triple antibiotic paste (TAP, 1 mg/mL). All medicaments, except for the positive controls, were allocated according to the light exposure protocol (ie, photoactivation with a light-emitting diode every 30 seconds for 4 minutes or without photoactivation). After treatment, the medicaments were removed, and 1 mL saline solution was added; the biofilm was scraped from the well and used to prepare a 1:2000 dilution. Spiral plating was performed using anaerobic blood agar plates. After 24 hours, colony-forming units (colony-forming units/mL, n = 11/group) were counted to determine the antimicrobial effects. Results: Data exhibited significant antimicrobial effects on the positive control groups followed by the curcumin irrigants and, lastly, the photoactivated curcumin-modified fibers. There was a significant reduction of viable bacteria in curcumin-based irrigants, which was greater than the TAP-treated group. Curcumin-free fibers, saline, and the nonphotoactivated curcumin-modified fibers did not display antimicrobial activity. Conclusions: Curcumin seems to be a potential alternative to TAP when controlling infection, but it requires a minimal concentration (2.5 mg/mL) to be effective. Photoactivation of curcumin-based medicaments seems to be essential to obtain greater antibiofilm activity.
Article
Full-text available
Cells are inhomogeneously crowded, possessing a wide range of intracellular liquid droplets abundantly present in the cytoplasm of eukaryotic and bacterial cells, in the mitochondrial matrix and nucleoplasm of eukaryotes, and in the chloroplast’s stroma of plant cells. These proteinaceous membrane-less organelles (PMLOs) not only represent a natural method of intracellular compartmentalization, which is crucial for successful execution of various biological functions, but also serve as important means for the processing of local information and rapid response to the fluctuations in environmental conditions. Since PMLOs, being complex macromolecular assemblages, possess many characteristic features of liquids, they represent highly dynamic (or fuzzy) protein–protein and/or protein–nucleic acid complexes. The biogenesis of PMLOs is controlled by specific intrinsically disordered proteins (IDPs) and hybrid proteins with ordered domains and intrinsically disordered protein regions (IDPRs), which, due to their highly dynamic structures and ability to facilitate multivalent interactions, serve as indispensable drivers of the biological liquid–liquid phase transitions (LLPTs) giving rise to PMLOs. In this article, the importance of the disorder-based supramolecular fuzziness for LLPTs and PMLO biogenesis is discussed.
Article
Full-text available
Three photodynamic therapy (PDT) protocols with 15 min, 3 h and 72 h drug-to-light time intervals (DLIs) were performed using a bacteriochlorin named redaporfin, as a photosensitizer. Blood flow and pO2 changes after applying these protocols were investigated in a Lewis lung carcinoma (LLC) mouse model and correlated with long-term tumor responses. In addition, cellular uptake, cytotoxicity and photocytotoxicity of redaporfin in LLC cells were evaluated. Our in vitro tests revealed negligible cytotoxicity, significant cellular uptake, generation of singlet oxygen, superoxide ion and hydroxyl radicals in the cells and changes in the mechanism of cell death as a function of the light dose. Results of in vivo studies showed that treatment focused on vascular destruction (V-PDT) leads to a highly effective long-term antineoplastic response mediated by a strong deprivation of blood supply. Tumors in 67% of the LLC bearing mice treated with V-PDT regressed completely and did not reappear for over 1 year. This significant efficacy can be attributed to photosensitizer (PS) properties as well as distribution and accurate control of oxygen level and density of vessels before and after PDT. V-PDT has a greater potential for success than treatment based on longer DLIs as usually applied in clinical practice.
Article
Full-text available
Photodynamic therapy (PDT) based periodontal disease treatment has received extensive attention. However, the deep tissue location of periodontal plaque makes the conventional PDT encounter a bottleneck. Herein, upconversion fluorescent nanomaterial with near-infrared light excitation was introduced into the treatment of periodontal disease, overcoming the limited tissue penetration depth of visible light in PDT. Photosensitizer Ce6 molecules were combined with upconversion nanoparticles (UCNPs) NaYF4:Yb,Er with a novel strategy. The hydrophobic UCNPs were modified with amphiphilic silane, utilizing the hydrophobic chain of the silane to bind to the hydrophobic groups of the UCNPs through a hydrophobic-hydrophobic interaction, and the Ce6 molecules were loaded in this hydrophobic layer. This achieves both the conversion of the hydrophobic to the hydrophilic surface and the loading of the oily photosensitizer molecules. Because the excitation position of the Ce6 molecule is in the red region, Mn ions were doped to enhance red light, and thus the improved PDT function. This Ce6 loaded UCNPs composites with efficient red upconversion luminescence show remarkable bacteriological therapeutic effect on Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum and the corresponding biofilms under 980 nm irradiation, indicating a high application prospect in the treatment of periodontal diseases.
Article
Full-text available
Photodynamic Therapy (PDT) has become one of the most promising treatment against autoimmune diseases, such as rheumatoid arthritis (RA), as well as in the treatment of different types of cancer, since it is a non-invasive method and easy to carry out. The three main ingredients of PDT are light irradiation, oxygen, and a photosensitizer (PS). Light irradiation depends on the type of molecule or compound to be used as a PS. The concentration of O2 fluctuates according to the medium where the target tissue is located and over time, although it is known that it is possible to provide oxygenated species to the treated area through the PS itself. Finally, each PS has its own characteristics, the efficacy of which depends on multiple factors, such as solubility, administration technique, retention time, stability, excitation wavelength, biocompatibility, and clearance, among others. Therefore, it is essential to have a thorough knowledge of the disease to select the best PS for a specific target, such as RA. In this review we will present the PSs used in the last three decades to treat RA under PDT protocol, as well as insights on the relevant strategies.
Article
Full-text available
Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current ‘greener’ methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.
Article
Full-text available
Fresh-cut fruits and vegetables are the main sources of foodborne illness outbreaks with implicated pathogens such as Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes. This study aimed at investigating the influence of two key parameters (concentration of curcumin and illumination time) on the effects of curcumin-based photodynamic sterilization on the preservation of fresh-cut Hami melons. The results indicated that illumination with 50 μmol/L curcumin for 60 min using a blue LED lamp reduced the total aerobic microorganism count by ~1.8 log CFU/g in fresh-cut Hami melons. Besides this, the effects of photodynamic sterilization on the soluble solids content, color, water content, firmness, and sensory indices of the fresh-cut Hami melons were also evaluated. Compared to the control group, photodynamic sterilization can effectively delay the browning rate and maintain the luminosity, firmness, water content, and soluble solids content of fresh-cut Hami melon. The sensory quality was indeed preserved well after 9 days of storage in a fridge. These results showed that photodynamic sterilization is an effective and promising technology to prolong the shelf life of fresh-cut Hami melons.
Article
Full-text available
Objective: The aim of this review is to discuss and compare the extensive range of biomedical applications of photo- and sono-activated Rose Bengal (RB). Background data: RB is a xanthene dye that due to its interesting photo- and sono-sensitive properties is gaining attention in the scientific field. Methods: This study is a literature review using the database PubMed. Results: As a photosensitizer, RB converts the triplet oxygen molecule into reactive oxygen species after irradiation with green light (532 nm). This mechanism allows for the use of photo-activated RB in photochemical tissue bonding, photodynamic therapy, antimicrobial therapy and cancer treatment, photothrombotic animal models, and other applications, including tissue engineering and treatment of tauopathies. As a sono-sensitive compound, RB is applied for sonodynamic therapy, cancer treatment, and antimicrobial therapy. Conclusions: This review outlines the versatility and effectiveness of photo- and sono-activated RB in numerous biomedical applications.
Article
Full-text available
Purpose Study on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers. Methods The concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum chemistry computations were performed for clarifying the origin of curcumin solubility enhancement in NADES. Results NADES comprising choline chloride and glycerol had the highest potential for curcumin dissolution. This system was also successfully applied as an extraction medium for obtaining curcuminoids from natural sources, as well as an effective stabilizer preventing curcumin degradation from sunlight. The solubility of curcumin in simulated gastrointestinal fluids revealed that the significant increase of bioavailability takes place in the small intestinal fluid. Conclusions Suspension of curcumin in NADES offers beneficial properties of this new liquid drug formulation starting from excreting from natural sources, through safe storage and ending on the final administration route. Therefore, there is a possibility of using a one-step process with this medium. The performed quantum chemistry computations clearly indicated the origin of the enhanced solubility of curcumin in NADES in the presence of intestinal fluids. Direct intermolecular contacts leading to hetero-molecular pairs with choline chloride and glycerol are responsible for elevating the bulk concentration of curcumin. Choline chloride plays a dominant role in the system and the complexes formed with curcumin are the most stable among all possible homo- and hetero-molecular pairs that can be found in NADES-curcumin systems.
Article
Full-text available
The search for novel anti-infectives is one of the most important challenges in natural product research, as diseases caused by bacteria, viruses, and fungi are influencing the human society all over the world. Natural compounds are a continuing source of novel anti-infectives. Accordingly, curcumin, has been used for centuries in Asian traditional medicine to treat various disorders. Numerous studies have shown that curcumin possesses a wide spectrum of biological and pharmacological properties, acting, for example, as anti-inflammatory, anti-angiogenic and anti-neoplastic, while no toxicity is associated with the compound. Recently, curcumin’s antiviral and antibacterial activity was investigated, and it was shown to act against various important human pathogens like the influenza virus, hepatitis C virus, HIV and strains of Staphylococcus, Streptococcus, and Pseudomonas. Despite the potency, curcumin has not yet been approved as a therapeutic antiviral agent. This review summarizes the current knowledge and future perspectives of the antiviral, antibacterial, and antifungal effects of curcumin.
Article
Full-text available
Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the quest for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Curcumin, the active ingredient of the Curcuma longa plant, has received great attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In this review, a summary of the medicinal chemistry and pharmacology of curcumin and its derivatives in regard to anticancer activity, their main mechanisms of action, and cellular targets has been provided based on the literature data from the experimental and clinical evaluation of curcumin in cancer cell lines, animal models, and human subjects. In addition, the recent advances in the drug delivery systems for curcumin delivery to cancer cells have been highlighted.
Article
Full-text available
Background: Curcumin and resveratrol are naturally occurring polyphenols that are highly effective in inhibiting the growth of cancer cells. A robust reversed-phase HPLC method has been developed for the simultaneous determination of these two natural drugs. Objective: The method was adapted to analyze both drugs in pure forms, in lipidic nanoemulsion formulation as well as in rat plasma. The method was applied to real samples after intravenous (IV) injection of rats. Method: Analysis utilized C18 column using acetonitrile (ACN)-water (pH adjusted to 4.6 by 1% orthophosphoric acid) in the ratio of 55+45 (v/v) at a flow rate of 0.8 mL/min with detection at 425 and 304 nm for curcumin and resveratrol, respectively. Results: Extraction efficiency of curcumin and resveratrol using ACN-methanol was 96.10-101.00% (RSD 2.49) and 95.00-99.87% (RSD 2.59), respectively. The assay was linear from 0.05 to 4.00 μg/mL (correlation coefficient of 0.9989 and 0.9981, respectively) and precise [average interday and intraday precision for curcumin RSD% (0.45, 2.04) and resveratrol RSD% (2.25, 1.71)] in spiked rat plasma. The LOD and LOQ were found to be (0.0085 μg/mL, 0.025 μg/mL) and (0.02, 0.06), respectively. Conclusions: The data presented demonstrate that the method provides rapid, sensitive, and precise determination of curcumin and resveratrol in spiked rat plasma and in nanoemulsion dosage form without tedious cleanup procedure, which was successfully applied for quantitation of both drugs following their IV administration to albino rats. Highlights: Validated chromatographic method has been developed for simultaneous determination of curcumin and resveratrol. Optimization of chromatographic conditions was achieved. Application of the method on nanoemulsion formula, on spiked rat plasma, and pharmacokinetics study.
Article
Full-text available
Periodontitis is a common infectious disease characterized by loss of tooth-supporting structures, which eventually leads to tooth loss. The heavy burden of periodontal disease and its negative consequence on the patient’s quality of life indicate a strong need for developing effective therapies. According to the World Health Organization, 10–15% of the global population suffers from severe periodontitis. Advances in understanding the etiology, epidemiology and microbiology of periodontal pocket flora have called for antibacterial therapeutic strategies for periodontitis treatment. Currently, antimicrobial strategies combining with polymer science have attracted tremendous interest in the last decade. This review focuses on the state of the art of antibacterial polymer application against periodontal pathogens and biofilms. The first part focuses on the different polymeric materials serving as antibacterial agents, drug carriers and periodontal barrier membranes to inhibit periodontal pathogens. The second part reviews cutting-edge research on the synthesis and evaluation of a new generation of bioactive dental polymers for Class-V restorations with therapeutic effects. They possess antibacterial, acid-reduction, protein-repellent, and remineralization capabilities. In addition, the antibacterial photodynamic therapy with polymeric materials against periodontal pathogens and biofilms is also briefly described in the third part. These novel bioactive and therapeutic polymeric materials and treatment methods have great potential to inhibit periodontitis and protect tooth structures.
Article
Full-text available
To our knowledge, there is still no evidence in relation to the combination of curcumin with chelants to improve the effects of antimicrobial photodynamic therapy (aPDT) on complex dental caries biofilms. Therefore, the aim of this study was to evaluate the antimicrobial effect of curcumin-ethylenediaminetetraacetic acid (EDTA)-mediated aPDT on the vitality of intact biofilms of dentin caries microcosms. Biofilms were grown on glass slabs in McBain medium plus 1% sucrose in microaerophily at 37 °C for 5 days. Then, biofilms were treated with associations of 600 μmol L⁻¹ curcumin combined or not with 1% EDTA and 37.5 or 75 J cm⁻² LED (455 nm). The vitality was determined by a confocal laser scanning microscopy (CLSM) after staining biofilms with a mixture of 2.5 g L⁻¹ fluorescein diacetate and 0.25 g L⁻¹ ethidium bromide. Statistical analysis was conducted by Kruskal-Wallis and post hoc Dunn’s test (P < 0.05). Three treatments were able to reduce the vitality of overall biofilms: curcumin + 75 J cm⁻² LED, curcumin-EDTA + 37.5 J cm⁻² LED, and curcumin-EDTA + 75 J cm⁻² LED. Also, the vitality of inner layers of biofilms was significantly reduced only after the combination of aPDT with EDTA. Therefore, the association of curcumin and EDTA improved the antimicrobial effect of aPDT on dentin caries microcosms, considering the application of lower light densities and deeper layers of biofilms.
Article
Full-text available
Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.
Article
Curcuma longa (CT) and Curcuma amada (MG) oleoresins were extracted using supercritical fluid extraction (SCF). SCF conditions were optimized for maximum extraction of oleoresin, curcuminoids, and total volatiles from CT at 350 bar/65 °C/150 min, and for maximum antioxidant and anti-inflammatory properties from MG at 300 bar/40 °C/30 min. Addition of 30% (v/w) ethanol as modifier improved the yield and activity in CT and MG, respectively, which was further improved upon enzymatic pretreatment with Stargen®002. Oleoresins were then subjected to FTIR and LC-HRMS analysis to determine the differences in their profile. MG contains phenolic acids and volatiles in addition to curcuminoids. In vitro comparative therapeutic assessment of CT and MG oleoresins revealed CT to have better bioactivity than MG which may be attributed to high concentration of curcuminoids. However, in vivo anti-inflammatory potential with respect to carrageenan induced paw edema model in rats showed MG to be better than CT. A combination of MG oleoresin with alum showed the highest anti-inflammatory capacity as compared to the standard drug, diclofenac. Thus, this study provides a phytochemical insight into the differences in Curucma species that might be responsible for the therapeutic activity rendered by the spices in vitro and in vivo.
Article
Gram-negative bacteria and bacteria in biofilms are very difficult to eradicate and are at the origin of the most antibiotic-resistant bacteria. Therapeutic alternatives less susceptible to mechanisms of resistance are urgently needed to respond to an alarming increase of resistant nosocomial infections. Antibacterial photodynamic inactivation (PDI) generates oxidative stress that triggers multiple cell death mechanisms more difficult to counteract by bacteria. We explore PDI of multidrug-resistant bacterial strains collected from patients and show how positive charge distribution in the photosensitizer drug impacts on the efficacy of inactivation. We demonstrate the relevance of size for drug diffusion in biofilms. Designed meso-imidazolyl porphyrins of small size with positive charges surrounding the macrocycle enabled the inactivation of bacteria in biofilms by 6.9 log units at 5 nM photosensitizer concentration and 5 J cm–2, which offers new opportunities to treat biofilm infections.
Article
Photodynamic therapy (PDT) is an approved medical technique to treat certain forms of cancer. It has been used to complement traditional anticancer modalities such as surgery, chemotherapy or radiotherapy, and in certain cases, to replace these treatments. One critical parameter of PDT is the photosensitizer (PS); historically, a purely organic macrocyclic tetrapyrrole-based structure. This short review surveys two recent clinical examples of metal complexes, namely TOOKAD®-Soluble and TLD-1433, which have ideal photophysical properties to act as PDT PSs. We highlight the important role played by the metal ions in the PS for PDT activity.
Article
In this study, the optimal parameters for the photodynamic inactivation (PDI) of Staphylococcus aureus in bacterial suspensions and in cheese were assessed using a water-soluble curcumin salt as the photosensitizer (PS). The in vitro study aimed on finding the optimal concentration and light dose to promote S. aureus photokilling. Four main groups were proposed: CONTROL (L-C-), LIGHT (L+C-), CUR (L-C+) and PDI (L+C+). A fixed light dose (LED, 450 ± 10 nm, 10 J · cm −2) was applied using four different PS concentrations (0.75, 1.0, 1.5 and 3.0 mg · mL −1). The dose also varied from 10 − 100 J · cm −2 for a fixed concentration. High inactivation rates were observed for all light doses, with a maximum reduction of 7.58 log 10 at 100 J · cm −2 (p 0.05). Saturation of the PDI effect was observed after a 10-minute illumination, as well as a slight decrease on the S. aureus population for increasing illumination times in the L+C-group. As an application, the concentration showing the best decontamination performance in vitro (0.75 mg · mL −1) was applied to decontaminate cheese in loco. PDI in two types of coalho cheese, a rennet-coagulated cheese commonly consumed in Brazil, was investigated. The results showed no significant inactivation in unpasteurized cheese, but a 4.34 log 10 reduction for t > 5 min in pasteurized specimens. In conclusion , the present PDI-catalyzed curcumin photosensitizer inactivated S. aureus at statistically significant levels in vitro, in pasteurized cheese, but not in unpasteurized specimens.
Article
Antimicrobial resistance is one of the most serious problems that researchers of multiple disciplines are working on. The number of new antibiotics and their targeted structures have continuously decreased emphasizing the demand of alternative therapy for bacterial infections. Photodynamic therapy is such a promising strategy that has been proven to be effective against a wide range of bacterial strains. In this study, an inhalable nanoformulation for photodynamic therapy against respiratory infections was developed in the form of nano-in-microparticles consisting of curcumin nanoparticles embedded in a mannitol matrix. The produced nano-in-microparticles exhibited suitable aerodynamic properties with a mass median aerodynamic diameter of 2.88 ± 0.13 µm and a high fine particle fraction of 60.99 ± 9.50 %. They could be readily redispersed in an aqueous medium producing the original nanoparticles without any substantial changes in their properties. This was confirmed using dynamic light scattering and electron microscopy. Furthermore, the redispersed nanoparticles showed an efficient antibacterial photoactivity causing 99.99992 % (6.1 log10) and 97.75 % (1.6 log10) reduction in the viability of Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha respectively. Based on these findings, it can be concluded that nano-in-microparticles represent promising drug delivery systems for antimicrobial photodynamic therapy.
Article
Background: There is still no systematized evidence in the literature regarding the combination of curcumin to improve the effects of antimicrobial photodynamic therapy (aPDT) on complex oral biofilms. Therefore, the objective of this review was to systematically assess the antimicrobial effect of curcumin-mediated aPDT on the vitality of biofilms of microorganisms Streptococcus mutans and Candida albicans. Methods: The addressed focused question was: "What are the effects of curcumin-mediated antimicrobial therapy on the biofilm viability of Streptococcus mutans and Candida albicans in vitro models?" A literature search was conducted in the electronic databases Pubmed, Web of Science, Scopus, Cochrane Library and Bireme up to April 2019. In vitro studies evaluating the effect of curcumin-mediated antimicrobial photodynamic therapy on S. mutans and C. albicans biofilms were included. Results: From 95 citations, 11 full-text articles were screened and 6 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible. Conclusions: The in vitro studies indicate the potential use of curcumin-mediated aPDT to inactivate microorganisms; Streptococcus mutans and Candida albicans. This survey should be viewed as a starting point for further examinations using standardized parameters to enhance outcomes.
Article
Background: The aim of this study was to determine the influence of distinct pre-irradiation times (PIT) of curcumin on the effectiveness of antimicrobial photodynamic therapy (aPDT) against intact dentin caries biofilms grown for 3 or 5 days. Methods: The microcosm biofilms grew on non-fluorescent glass blocks immersed in McBain medium with 1% sucrose, using microaerophilic conditions at 37 °C for 3 or 5 days. The biofilms were treated by the association of 600 μmol.L-1 curcumin using different pre-irradiation times (1, 2 or 5 min) combined with 0 or 75 J.cm-2 blue LED. Then, the vitality of biofilms was determined by confocal scanning laser microscopy (CSLM), after being stained with the mixture of ethidium bromide and fluorescein diacetate. Statistical analysis was performed by two-way ANOVA and post-hoc Tukey tests, after arcsine transformation (P < 0,05). Results: In comparison to control, curcumin alone (PIT = 5 min) and all combinations of curcumin and LED reduced significantly the vitality of 3-day biofilms. Distinctly, only curcumin plus LED using PITs of 2 or 5 min were effective in reducing the vitality of 5-day biofilms. Conclusion: Curcumin-mediated aPDT significantly decreased the vitality of intact dentin caries microcosms grown during 3 or 5 days, although successful treatments of 5-day biofilms required longer PITs in comparison to their counterparts.
Article
Staphylococcus aureus are multiresistant pathogens that causes superficial and systemic infections. Antimicrobial photodynamic therapy (APDT) is an alternative in the treatment of diseases caused by these bacteria. Aim: In this study the APDT response on growth, viability, formation of reactive oxygen species and adhesion of methicillin sensitive strains of Staphylococcus aureus, methicillin resistant strains of S. aureus and American type culture collection (ATCC) of S. aureus were evaluated in vitro, after incubation with curcumin for 20 min, and irradiated with LED.Materials & methods: Bacterial growth was assessed by the number of colony forming units, viability and adhesion were evaluated by confocal microscopy and ROS quantification was performed by fluorimetry. Results: Was observed increase in the production of ROS in APDT groups, besides a decrease in the 4 log growth and loss of the bacterial adhesion. Conclusion: APDT with Curcumin may be an interesting therapeutic alternative, due to its in vitro response, in the control multiresistant clinical S. aureus strains.
Article
The focus of this review is to describe the state-of-art in the development of innovative drug delivery systems for phthalocyanines as photosensitizers for photodynamic therapy (PDT). PDT is a medical treatment combining photosensitizers (PSs) activated by visible light of a specific wavelength to selectively destroy targeted cells, tumor tissues and its surrounding vasculature. In the last decades, PDT has been under intense investigation, first as a promising alternative approach for improved cancer treatment, later against microbial infection and nowadays, mainly in aesthetic medicine, against age-related degeneration. The success of PDT is restricted because of difficulties with administration and skin permeation of PSs. As PDT importance raises, there is high interest for advanced formulations and delivery systems (DDS) for PS, especially formulations based on nanotechnology. Accordingly, this review deals with the innovations pertaining to DDS for PDT as disclosed in recent patents and literature.
Article
Background: Canida albicans can cause opportunistic infections ranging from superficial mucous membrane lesions to life-threatening disease. The aim of this study is to investigate the antifungal effect of photodynamic therapy (PDT) mediated by curcumin (CUR) on C. albicans biofilms in vitro. Methods: One standard strain ATCC 90028 and two clinical isolates from HIV (CCA1) and oral lichen planus (CCA2) patients' oral cavities were used in this study. Biofilms were photosensitized with 60 μM CUR and irradiated by light emitting diode (LED) under the wavelength of 455 nm and energy densities of 2.64, 5.28, 7.92, 10.56, 13.2 J/cm2. Then the antifungal effects of CUR-PDT were evaluated by XTT reduction assay and confocal light scanning microscopy (CLSM) observations. The effects of CUR-PDT on the expression levels of hypha-specific and biofilm-related genes including EFG1, UME6, HGC1 and ECE1 were assessed by quantitative Real-time PCR (qRT-PCR) method. Results: The inhibition rates after CUR-PDT in three biofilms(ATCC 90028, CCA1, CCA2)were 90.87%, 66.44% and 86.74% respectively (p < 0.05). Relative gene expression levels of EFG1, UME6, HGC1 and ECE1 were all downregulated after CUR-PDT, with fold-decrease of 6.865, 3.382, 2.167 and 6.887 in ATCC 90028, 2.466, 2.146, 1.627 and 3.102 in CCA1, and 5.406, 2.347, 2.073and 3.711 in CCA2 (p < 0.05). Conclusions: Curcumin-mediated PDT could effectively inactivateCandida albicans biofilms in vitro. Expression of genes involved in biofilms formation were downregulated after CUR-PDT.
Article
An increasing interest on atorvastatin and curcumin due to their potential anticancer activity. A new, accurate and sensitive HPLC method was developed, for the first time, to simultaneously quantify atorvastatin and curcumin in mice plasma and brain, liver, lung and spleen tissues following a protein precipitation sample preparation. The chromatographic separation was achieved in 13 min on a C18 column, at 35°C, using a mobile phase composed of acetonitrile‐methanol‐2 % (v/v) acetic acid (37.5:2.5:60, v/v/v) at a flow rate of 1.0 mL/min. The detection of analytes and internal standard was carried out at 247 nm, 425 nm and 250 nm, respectively. According to international guidelines, the method showed to be selective, with lower limits of quantification ranging from 10 to 500 ng/mL for curcumin, and from 100 to 600 ng/mL for atorvastatin, linear over a wide concentration range (r2 ≥ 0.9971) and with acceptable accuracy (bias ± 12.29%) and precision (coefficient of variation ≤ 13.15%). The analytes were reproducibly recovered at a percentage higher than 81.10% and demonstrated to be stable on several experimental conditions in all biological matrices. This method can be easily applied to in vivo biodistribution studies related to the intranasal administration of atorvastatin and curcumin, separately or simultaneously.
Article
The present review illustrates the state of the art in the field of liquid chromatography (LC) hyphenated to electron ionization mass spectrometry (EI MS). An overview of applications over the last decades is given, in order to demonstrate the benefits arisen from the use of EI for the characterization of typically LC-amenable samples. Key advantages are related to the extensive fragmentation pattern useful for structure elucidation and the absence of matrix effects, differently from the most commonly employed LC-MS interfaces (e.g., electrospray). Different interfaces which made the LC-EI MS coupling feasible are described, along with several approaches proposed to overcome well-known incompatibility issues.
Article
Fluorescence spectroscopy may assisst in the diagnosis and control of infectious processes associated with bone lesions of the oral cavity. The aim of this study was to analyze, through fluorescence spectroscopy, Candida albicans biofilms formed in artificial bone cavities treated with photodynamic therapy (PDT)mediated with 450-nm blue light-emitting diode (LED)and curcumin. Another aim of this study was to analyze the existence of a correlation between the effectiveness of the photodynamic treatments and the fluorescence spectroscopy images. Artificial bone lesions (n = 40)were made in bovine bones and inoculated with standard suspensions of Candida albicans (ATCC 18804)for biofilm formation (14 days / 36 °C ± 1 °C). The 40 specimens were distributed among four experimental groups (n = 10): L-C- (control), L + C- (LED for 5 min), L-C+ (curcumin for 5 min), and L + C+ (PDT). Aliquots of 100 μL were collected from the bone cavities after treatments and were seeded in duplicate on Sabouraud dextrose agar for 24 h at 36 °C ± 1 °C and the colony-forming units (CFU/ mL)were counted. Before and after each treatment, the specimens were subjected to spectral fluorescence and the images were compared using the Image J program. The log 10 CFU/mL were compared with Kruskal-Wallis and Dunn's Multiple Comparison post-test (significance level at 0.05). The fluorescence histogram values before and after treatment were compared using Wilcoxon test (95%).The correlation between Candida albicans log 10 CFU/mL and the number of the fluorescence red pixels spectroscopy was verified using Spearman correlation test. The reduction of Candida albicans log 10 CFU/mL in the L + C+ (PDT)group was the most relevant and the fluorescence spectroscopy was correlated to the microbiological result. It was concluded that there was a consistency between the number of Candida albicans log 10 CFU/mL and the red pixel data of the fluorescence images, demonstrating that the fluorescence diagnostic device reflects the true microbiological condition of Candida albicans biofilms in the bone cavities during the pre-treatment and post-treatment, thus providing the clinician the ability to dynamically, simply, and instantaneously verify the performance of the treatment used.
Article
This study evaluated the effect of antimicrobial photodynamic therapy (aPDT) on S. mutans using diacetylcurcumin (DAC) and verified DAC toxicity. In vitro, S. mutans biofilms were exposed to curcumin (CUR) and DAC and were light-irradiated. Biofilms were collected, plated and incubated for colony counts. DAC and CUR toxicity assays were conducted with Human Gingival Fibroblast cells (HGF). In vivo, G. mellonella larvae were injected with S. mutans and treated with DAC, CUR and aPDT. The hemolymph was plated and incubated for colony counts. Significant reductions were observed when DAC and CUR alone were used and when aPDT was applied. HGF assays demonstrated no differences in cell viability for most groups. DAC and CUR reduced the S. mutans load in G. mellonella larvae both alone and with aPDT. Systematic toxicity assays on G. mellonella demonstrated no effect of DAC and CUR or aPDT on the survival curve.
Article
Nowadays, both cancer and infections caused by antibiotic resistant microorganisms are problems that affect the entire planet. Phototherapy (namely photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms) are an alternative method for the treatment of these diseases. That requires adequate photosensitizers and, in this sense, boron-dipyrromethenes (BODIPYs) have interesting properties to act as phototherapeutic agents. In the present review, first, we describe the different strategies used to increase reactive oxygen species production. Then, we explain different architectures developed aiming to enhance the solubility of BODIPYs in biological media in order to optimize their targeting and delivery into the cells to be treated. Finally, we discuss the design of BODIPYs that are activated by specific stimuli present in the target tissues, allowing increasing the selectivity of the treatment. The data presented and discussed here show that BODIPYs are outstanding photosensitizers for the treatment of tumors and infections in the presence of oxygen and light.
Article
The multi-drug resistant bacteria have become a serious problem complicating therapies to such a degree that often the term “post-antibiotic era” is applied to describe the situation. The infections with methicillin-resistant S. aureus, vancomycin-resistant E. faecium, third generation cephalosporin-resistant E. coli, third generation cephalosporin-resistant K. pneumoniae and carbapenem-resistant P. aeruginosa have become commonplace. Thus, the new strategies of infection treatment have been searched for, and one of the approaches is based on photodynamic antimicrobial chemotherapy. Photodynamic protocols require the interaction of photosensitizer, molecular oxygen and light. The aim of this review is to provide a comprehensive overview of photodynamic antimicrobial chemotherapy by porphyrinoid photosensitizers. In the first part of the review information on the mechanism of photodynamic action and the mechanism of the bacteria resistance to the photodynamic technique were described. In the second one, it was described porphyrinoids photosensitizers like: porphyrins, chlorins and phthalocyanines useable in photodynamic bacteria inactivation.
Article
The objective of this study was to evaluate the bactericidal effect of curcumin (CUR)-mediated photodynamic inactivation (PDI) against Escherichia coli DH5α in vitro and in oysters, then further investigate the edible security of PDI-treated oysters based on cellular toxicological methods. First, DH5α cells were irradiated by a 470 nm LED light source with an energy density of 3.6 J/cm ² . Colony forming units (CFU) were counted and the viability of DH5α cells was calculated after treatment with CUR-mediated PDI. Intracellular production of reactive oxygen species (ROS) was studied by measuring the fluorescence of 2, 7-dichlorofluorescein (DCF) using a flow cytometry. Membrane permeability was measured using confocal laser scanning microscopy (CLSM) with propidium iodide (PI) staining. After that, the bactericidal effect of CUR-mediated PDI was evaluated in oysters which were pre-contaminated with DH5α cells. Finally, cellular toxicology of PDI-treated oysters was evaluated through morphological observation, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, DNA ladder assay, and nuclear staining. Results showed that the viability of DH5α was significantly decreased in a CUR concentration-dependent manner and resulted in an approximately 3.5-log reduction at the concentration of 20 μM. After treatment with CUR-mediated PDI (20 μM, 3.6 J/cm ² ), the ROS level in DH5α cells and the membrane permeability markedly increased. Our data demonstrated that CUR-mediated PDI had a good decontamination effect against DH5α contaminated in oysters. After incubation with PDI-treated oysters, fibroblasts L929 cell morphology, MTT absorbance and cell apoptosis had no obvious changes. Our findings preliminarily demonstrated that CUR-mediated PDI-treated oysters had no cytotoxicity to fibroblasts.
Article
The constant increase in multi-resistant bacterial strains and the decline in the number of newly approved antibiotics necessitate the development of alternative approaches to antibiotic treatment. In this study, a modern alternative approach to antibiotic therapy using photosensitiser encapsulated polymeric nanoparticles is presented. Cationic nanoparticles were prepared using a biodegradable and biocompatible polymer poly (lactic-co-glycolic acid), a stabiliser poly (vinyl alcohol) and chitosan. Dynamic light scattering and laser Doppler anemometry were used to determine particle size distribution and ζ-potential respectively. To quantify the antibacterial photodynamic effect of the nanoparticles, in vitro studies were performed using Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha to represent both a gram-positive as well as a gram-negative strain. It was demonstrated, that the particle ζ-potential significantly influenced the antibacterial phototoxicity, gaining up to 3 log10 higher efficacy for chitosan coated nanoparticles. Furthermore, neither irradiation alone nor curcumin in absence of light led to a significant growth reduction, confirming the photodynamic effect of curcumin. Electron microscopy has been used to study the morphological characteristics of the nanoparticles as well as their interaction with bacteria and the changes of bacterial morphology and ultrastructure upon photodynamic treatment. An increased adherence of the chitosan modified nanoparticles to the bacteria and structural damage upon photodynamic treatment was clearly evident and confirmed the results from in vitro studies.
Article
Background: Antimicrobial photodynamic therapy (aPDT) is a growing approach to treat skin and mucosal infections. Despite its effectiveness, investigators have explored whether aPDT can be further combined with antibiotics and antifungal drugs. Objective: To systematically assess the in vivo studies on the effectiveness of combinations of aPTD plus antimicrobials in the treatment of cutaneous and mucosal infections. Materials and methods: Searches were performed in four databases (PubMed, EMBASE, Cochrane library databases, ClinicaTrials.gov) until July 2018. The pooled information was evaluated according to the PRISMA guidelines. Results: 11 full-text articles were finally evaluated and included. The best aPDT combinations involved 5-aminolevulinic acid or phenothiazinium dye-based aPDT. In general, the combination shows benefits such as reducing treatment times, lowering drug dosages, decreasing drug toxicity, improving patient compliance and diminishing the risk of developing resistance. The mechanism of action may be that first aPDT damages the microbial cell wall or membrane, which allows better penetration of the antimicrobial drug. Limitations: The number of studies was low, the protocols used were heterogeneous, and there was a lack of clinical trials. Conclusions: The additive or synergistic effect of aPDT combined with antimicrobials could be promising to manage skin and mucosal infections, helping to overcome the microbial drug resistance.
Article
Aim To evaluate the capacity of carbopol gel to maintain the intensity of a LED curing light (blueLED) along the length of prepared root canals in bovine teeth, and to assess the antimicrobial capacity of curcumin photoactivated by a LED curing light in the presence of carbopol gel. Methodology Experiment 1: Eight straight roots of bovine incisors were standardized to a length of 15 mm, and the root canals instrumented up to a size 120 K‐file. The LED curing light was irradiated inside the root canals using an aluminium collimator (1.5mm in diameter) placed at the orifice (n=8). Initially, the irradiation was performed in empty root canals and then repeated with the root canals filled with carbopol gel. Simple standardized photographs of the roots were taken with a digital camera in the mesial perspective during the irradiation procedure and the images analysed in OriginLab software to verify the light intensity along the length of the root. Experiment 2: Twenty dentine blocks were obtained from the cervical third of bovine incisors using a trephine bur. Biofilms were induced for 21 days on the blocks using Enterococcus faecalis (ATCC 4083) at 10⁹ cells/mL. The blocks were treated according to the groups (n=5): positive control; standard PDT (methylene blue + diode Laser); curcumin; LED curing light; and curcumin + LED curing light. After the treatment, the samples were dyed with Live/Dead BacLight Bacterial Viability solution and fluorescence images were obtained by Confocal Scanning Laser Microscopy (CSLM). Experiment 3: Thirty‐two roots of bovine incisors were prepared as described in experiment 1. Their dentinal tubules were contaminated and the root canals treated according to the groups (n=8): positive control; standard PDT; curcumin + LED curing light; curcumin + carbopol gel + LED curing light. The specimens were sectioned longitudinally and the split roots were treated with the Live/Dead dye to obtain fluorescence images by CSLM. All images were processed using BioImageL software to measure the percentage of viable bacteria and the data analysed statistically using the non‐parametric Kruskal Wallis test (α<0.05). Results In Experiment 1, carbopol gel did not improve the intensity of LED light transmission along the root canal. In Experiment 2, a significant decrease (P <0.05) in bacterial viability occurred in the following order: positive control < only LED curing light < only curcumin < curcumin + LED curing light = standard PDT; and in Experiment 3 positive control = curcumin + LED curing light ≤ curcumin + gel + LED curing light ≤ standard PDT. Conclusion Similar disinfection effectiveness was obtained using curcumin + LED curing light and methylene blue + 660nm LASER (standard PDT). The use of carbopol gel did not favour a greater transmission of LED light along the root canal, and also resulted in less bacterial killing when used in endodontic PDT. This article is protected by copyright. All rights reserved.
Article
The potential of fluorescence spectroscopy is exploited for the characterization and comparison of different turmeric varieties based on curcuminoids content in turmeric powders. Fluorescence spectra from turmeric powders has been acquired by using excitation wavelengths from 300 to 470 nm with step of 10 nm to investigate the effect of excitation wavelengths on the emission of valuable ingredients for their characterization. Emission spectra revealed that fresh wet turmeric rhizomes show emission bands at 571 nm which is due to curcumin. It is found that main ingredient of turmeric powder is curcumin and best excitation wavelength is 467 nm for its maximum emission intensity. High Pressure Liquid Chromatography (HPLC) was used as alternate standard technique for determination of curcuminoid content in the reference samples. The curcumin content in the commercially available local turmeric brands were also evaluated, one brand showed significant covariance from standard fluorescent spectra of turmeric meaning this particular brand contained minimum curcumin content or have been severely adultered. In the next step the powders were heated at different temperatures from 60 °C to 150 °C (Normal cooking & frying temperatures) to observe the difference in emission spectra particularly keeping in view the molecular composition and curcuminoid content in turmeric. The results indicate that curcumin content gradually decreases above 90 °C. Principal component analysis (PCA) has been employed on all the data to statistically differentiate small molecular changes and adulteration by covariance calculations.
Article
Objective Conduct a PROSPERO registered (CRD42018105227) systematic review of the efficacy of curcumin in the treatment of oral lichen planus (OLP). Data sources Medline from the earliest possible date to the present (December 18, 2018) using the terms “turmeric” OR “curcumin” OR “curcuma“ AND “oral lichen planus“. Study selection and data extraction Studies assessing patient outcomes in OLP. There were four trials assessing the comparative efficacy of topical curcumin vs. topical corticosteroids and three trials assessing the efficacy of oral curcumin vs. placebo. Data synthesis Clinical and methodological heterogeneity precluded statistical pooling. There were many limitations in the literature weakening the strength and applicability of evidence. Topical curcumin provided reductions in pain, burning, and clinical manifestations of OLP versus baseline, effects similar or inferior to topical corticosteroids. In oral curcumin trials, there were no significant benefits of curcumin therapy versus placebo but there were some potential benefits and reasonable safety in an observational extension study. Conclusions It is difficult to determine whether topical or oral curcumin is a viable therapy for oral lichen planus. Topically applied curcumin in particular shows promising preliminary data but would likely not supplant topical corticosteroids as the modality of choice for most patients.
Article
Reversed-phase high-performance liquid chromatography (RP-HPLC) is the most popular chromatographic mode, accounting for more than 90% of all separations. HPLC itself owes its immense popularity to it being relatively simple and inexpensive, with the equipment being reliable and easy to operate. Due to extensive automation, it can be run virtually unattended with multiple samples at various separation conditions, even by relatively low-skilled personnel. Currently, there are >600 RP-HPLC columns available to end users for purchase, some of which exhibit very large differences in selectivity and production quality. Often, two similar RP-HPLC columns are not equally suitable for the requisite separation, and to date, there is no universal RP-HPLC column covering a variety of analytes. This forces analytical laboratories to keep a multitude of diverse columns. Therefore, column selection is a crucial segment of RP-HPLC method development, especially since sample complexity is constantly increasing. Rationally choosing an appropriate column is complicated. In addition to the differences in the primary intermolecular interactions with analytes of the dispersive (London) type, individual columns can also exhibit a unique character owing to specific polar, hydrogen bond, and electron pair donor–acceptor interactions. They can also vary depending on the type of packing, amount and type of residual silanols, “end-capping”, bonding density of ligands, and pore size, among others. Consequently, the chromatographic performance of RP-HPLC systems is often considerably altered depending on the selected column. Although a wide spectrum of knowledge is available on this important subject, there is still a lack of a comprehensive review for an objective comparison and/or selection of chromatographic columns. We aim for this review to be a comprehensive, authoritative, critical, and easily readable monograph of the most relevant publications regarding column selection and characterization in RP-HPLC covering the past four decades. Future perspectives, which involve the integration of state-of-the-art molecular simulations (molecular dynamics or Monte Carlo) with minimal experiments, aimed at nearly “experiment-free” column selection methodology, are proposed.
Article
Objectives: The objectives of this study were to: (1) develop the multifunctional nanoparticles containing Chlorin e6 (Ce6), Coumarin 6 (C6) and Fe3O4 nanoparticles (NPs); and (2) investigate the inhibitory effects of the nanoparticles via antibacterial photodynamic therapy (aPDT) against three species of periodontitis-related pathogens for the first time. Materials and methods: Ce6 and C6 were co-loaded into the Fe3O4-silane core-shell structure to form multifunctional nanoparticles (denoted "Fe3O4-silane@Ce6/C6 MNPs"). The physical and chemical properties of nanoparticles were characterized. Biofilm properties of Streptococcus sanguinis, Porphyromonas gingivalis and Fusobacterium nucleatum were tested. Colony-forming units (CFU), live/dead assay, and metabolic activity of biofilms were determined to evaluate the aPDT function mediated by the Fe3O4-silane@Ce6/C6 MNPs. Fluorescence imaging and the targeted antibacterial effects were also investigated. Results: Fe3O4-silane@Ce6/C6 MNPs showed superparamagnetic properties, chemical stability and water-solubility, with no cytotoxicity. Fe3O4 NPs did not compromise the emission peaks of C6 and Ce6. The Fe3O4-silane@Ce6/C6-mediated aPDT had much greater reduction in biofilms than the control groups (p < 0.05). Biofilm CFU was reduced by about 4-5 orders of magnitude via Fe3O4-silane@Ce6/C6-mediated aPDT. The co-loading of Ce6 and C6 enabled the real-time aPDT monitoring by ratio emissions with the same wavelength. Fe3O4 with magnetic field enabled the targeting of infection sites by killing bacteria via magnetic field. Conclusion: The multifunctional nanoparticles exerted strong anti-biofilm activity against periodontitis-related pathogens, with excellent biocompatibility, real-time monitoring, and magnetically-targeting capacities. The multifunctional nanoparticles have great potential in antibacterial applications to inhibit the occurrence and progression of periodontitis.
Article
In this study we evaluated the photolarvicidal activity of different curcuminoids forms: Natural Turmeric (NT), Synthetic Curcumin (SC) and Synthetic curcumin formulated with sucrose (SCS) against Aedes aegypti larvae which is the major vector of dengue, chikungunya and Zika viruses. Two strategies for curcuminoids delivery were chosen for the experiments: (i) larvae exposed to aqueous solutions of curcuminoids in the concentration range of 5–25 mg/L (w/v) and (ii) larvae exposed to two different types of curcuminoids carriers (pet food). Phototoxic effects of the curcuminoids were evaluated by counting the dead larvae after sunlight exposure, at irradiance range of 30–60 mW/cm². The characteristic photobleaching time for each curcuminoids in solution was also determined in order to infer the safety of these molecules in the natural environment. Curcuminoids solutions showed high photolarvicidal activity after 30 min of sunlight irradiation, with LC50 values of 20.0, 11.6 and 2.2 mg/L for NT, SC and SCS, respectively. The curcuminoids carriers, despite showing high mortality (about 90%), presented photodynamic activity only after 8 h of sunlight irradiation. The curcuminoids remained in the aqueous solution for up to 3 h; subsequently, the maximum absorption peak of these pigments was completely modified. The characteristic photobleaching time for each sample was 6, 32 and 60 min for NT, SC and SCS. These original and relevant results show that the combination of curcuminoids pigments with sunlight establishes an extremely effective alternative for Ae. aegypti larvae control, ensuring high environmental safety due to the low persistence of these molecules in the presence of light.
Article
Periprosthetic joint infection (PJI) with Methicillin-resistant Staphylococcus aureus (MRSA) is the catastrophic deep joint infection for patients after the joint replacement surgery. To efficiently eradicate the MRSA, we synthesized the curcumin-upconversion nanoparticles (curcumin-UCNPs) by binding the curcumin onto upconversion nanoparticles, which could produce singlet oxygen under the near infrared (NIR) irradiation. Dual antibacterial behaviors induced by curcumin-UCNPs themselves and induced by photodynamic therapy were demonstrated. Nearly 100% MRSA was eradicated by curcumin-UCNPs under the NIR irradiation due to the dual antibacterial behaviors in vitro. Furthermore, we constructed the MRSA-induced PJI model with SD rats. NIR could penetrate the rats knee joint tissue well and activate the curcumin-UCNPs to perform photodynamic therapy, which exhibited a good antibacterial effect in the deep joint tissue (1cm) and about 80% of MRSA was eradicated in vivo. Blood tests and histopathological examinations revealed that the inflammation also significantly relieved due to the eradication of MRSA in the curcumin-UCNPs-NIR group. Compared with traditional treatments , this research may provide a new way of therapy for PJI.
Article
Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru(II) polypyridyl complexes have emerged as promising systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state electronic configurations accessible with visible and near-infrared light, and these properties can be exploited for both energy- and electron-transfer processes that can yield highly potent oxygen-dependent and/or oxygen-independent photobiological activity. Selected examples highlight the use of rational design in coordination chemistry to control the lowest-energy triplet excited-state configurations for eliciting a particular type of photoreactivity for PDT and/or PCT effects. These principles are also discussed in the context of the development of TLD1433, the first Ru(II)-based photosensitizer for PDT to enter a human clinical trial. The design of TLD1433 arose from a tumor-centered approach, as part of a complete PDT package that includes the light component and the protocol for treating non-muscle invasive bladder cancer. Briefly, this review summarizes the challenges to bringing PDT into mainstream cancer therapy. It considers the chemical and photophysical solutions that transition metal complexes offer, and it puts into context the multidisciplinary effort needed to bring a new drug to clinical trial.
Article
Background: Despite the high success rate of endodontic treatment, failure may occur in some cases. In this case, Enterococcus faecalis is the most common species in endodontic treatment failure and post-treatment apical periodontitis. Therefore, a new adjunctive strategy is needed for the prevention of endodontic infections due to E. faecalis. The aim of the present study was to compare the antimicrobial and anti-biofilm activities of different common photosensitizers (PSs) for use in antimicrobial photodynamic therapy (aPDT) against E. faecalis. Materials and methods: E. faecalis strain ATCC 29212 was used as the tested strain and methylene blue (MB), toluidine blue O (TBO), indocyanine green (ICG), and curcumin (CUR) were used as PSs. Irradiation was carried out using diode laser and light emitting diode (LED) at wavelengths related to the above PSs. Then, antimicrobial and anti-biofilm activities were measured using the microbial viability assay and crystal violet test, respectively. Results: aPDT with using the above PSs significantly decreased the CFU/mL count of E. faecalis compared to the control group (P < 0.05). The killing percentage of E. faecalis via PS mediated aPDT was 99.6%, 98.2%, 85.1%, and 65.0% for CUR, ICG, TBO, and MB, respectively. aPDT using the above PSs significantly decreased the biofilm formation ability of E. faecalis compared to the control group (P < 0.05). The biofilm reduction percentage of the PSs was 68.4%, 62.9%, 59.0%, and 47.6% for CUR, ICG, TBO, and MB, respectively. Conclusion: CUR and ICG mediated aPDT exhibited considerably more antimicrobial activity than other PSs, while TBO and MB demonstrated weaker anti-biofilm effects against E. faecalis compared to other PSs.
Article
Propionibacterium acnes (P. acnes) is an opportunistic infection in human skin that causes acne vulgaris. Antibiotic agents provide the effective eradication of microbes until the development of drug-resistant microbes. Photodynamic inactivation (PDI) is a non-antibiotic therapy for microbial eradication. In this study, the visible blue light (BL, λmax = 462 nm) was used to enhance the antimicrobial activities of curcumin, a natural phenolic compound. Individual exposure to curcumin or BL irradiation does not generate cytotoxicity on P. acnes. The viability of P. acnes was decreased significantly in 0.09 J/cm2 BL with 1.52 μM of curcumin. Furthermore, the low-dose blue light irradiation triggers a series of cytotoxic actions of curcumin on P. acnes. The lethal factors of photolytic curcumin were investigated based on the morphology of P. acnes by SEM and fluorescent images. The membrane disruption of microbes was observed on the PDI against P. acnes. Chromatography and mass spectrometry techniques were also used to identify the photolytic metabolites. Curcumin could be photolysed into vanillin through BL irradiation, which presents a strong linear relationship in quantitation. Because the safety of blue light in mammalian cell has been proven, the photolytic curcumin treatment could support non-antibiotic therapy to eradicate P. acnes on clinical dermatology.