Curcumin-mediated Photodynamic Therapy Research Articles

Curcumin-mediated photodynamic therapy for mild to moderate Acne: A self-controlled split-face randomized study

ObjectiveTo evaluate the effectiveness and safety of Curcumin-mediated Photodynamic Therapy (Curcumin-PDT) in the treatment of mild to moderate acne. MethodsIn this randomized split-face controlled study, 11 patients with mild to moderate acne were randomly divided into two groups. One side received a single 445 nm LED light exposure of 36 J/cm2, while the other side received Curcumin-PDT. The process of Curcumin-PDT involves the application of a mask containing 1 % curcumin for 20 min, followed by exposure to 445 nm LED light at 36 J/cm². The treatment consists of sessions spaced every 3 days, with a total of 2 treatments per week, administered continuously for 2 weeks. Efficacy assessment and comparison were conducted on both groups of patients before treatment and 2 weeks after the last treatment, and adverse reactions were observed and recorded. ResultsAt the 2-week follow-up after the last treatment, the total lesion clearance rates for Curcumin-PDT and monotherapy light were 54.7 ± 21.5 % and 28.1 ± 19.9 %, respectively (P = 0.001). The clearance rates for non-inflammatory lesions were 32.3 ± 25.7 % and 21.9 ± 14.0 % for Curcumin-PDT and monotherapy light sides (P = 0.252), while for inflammatory lesions, the clearance rates were 59.3 ± 28.2 % and 36.5 ± 21.6 % (P = 0.013). Both groups experienced mild erythema after treatment, which subsided within 1–2 h. Two patients developed mild localized pigmentation, which self-resolved after 1 month of follow-up. Both groups did not exhibit edema, crust formation, scaling, pigment reduction, or scarring. ConclusionCurcumin-PDT can be considered a safe and effective method for the treatment of mild to moderate acne.

Efficacy of curcumin-mediated photodynamic therapy for root canal therapy procedures: A systematic review.

This systematic review aimed to investigate the effectiveness of CUR-mediated PDT (Curcumin mediated PDT) as an adjunct to conventional chemo-mechanical debridement and/or standard PDT of the RC system with endodontic infections. The focused research question was: "Whether the application Curcumin mediated PDT as an adjunct is more effective than the traditional chemo-mechanical debridement and/or standard PDT of the RC system alone for improving antibacterial and/or mechanical features among subjects undergoing RCT?". An electronic literature search was performed in Scopus, PubMed, and Web of Science. In vitro reports utilizing Curcumin mediated PDT as an adjunct to conventional chemo-mechanical debridement considering permanent dentition assessing the antibacterial and/or mechanical effect were included. Eighteen articles were included in the review, out of which 13 studies assessed the antibacterial activity, while 5 evaluated the mechanical properties. Most of the studies concluded that Curcumin mediated PDT had a significant antibacterial activity than the conventional chemo-mechanical debridement and/or standard PDT. Four of the five studies suggested that Curcumin mediated PDT had no impact on the push-out bond strength of root dentin. Furthermore, the significant heterogeneity in the data from the included studies did not permit the author to carry out a meta-analysis. There is potential for application of Curcumin mediated PDT as an adjunct to the conventional chemo-mechanical debridement and/or standard PDT in reducing the bacterial load, however, Curcumin mediated PDT has minimal effect on enhancing the pushout bond strength of fiber posts to radicular dentin. Moreover, clinical studies are required to provide a more conclusive opinion on the efficacy of Curcumin mediated PDT for RCT procedures.

Therapeutic efficacy of adjunctive photodynamic therapy in the treatment of denture stomatitis

BackgroundThe present report assessed the efficacy of curcumin-mediated photodynamic therapy (CUR-mediated PDT) as an adjunct to antifungal gel treatment by evaluating the salivary interleukin-6 (IL-6) and matrix metalloproteinases-8 (MMP-8) levels together with Candida species counts in denture stomatitis (DS) patients. MethodsIn total, 50 DS subjects were randomly categorized into 2 groups: Group-1: subjects who received the antifungal gel treatment and Group-2: participants who received CUR-mediated PDT. The Sabourad Dextrose Agar and CHROMAgar were utilized for evaluating Candida species counts, while the Enzyme-Linked Immunosorbent Assay was employed to estimate the salivary levels of IL-6 and MMP-8. All clinical evaluations were performed at the baseline, 1 month, and 2 months. ResultsIn total, group-2 subjects showed a significant decrease in Candida albicans (C. albicans) counts on both follow-ups (i.e., 1-month and 2-month) than group-1 participants. C. krusei count also reduced in group-2 subejcts than group-1 participants at the 2nd follow-up as compared to the baseline, nevertheless, a slight increase in C. krusei count was noticed in group-2 subjects at the 2nd follow-up than the 1st follow-up. The salivary IL-6 and MMP-8 levels in both groups reduced significantly at both follow-ups than the baseline. According to the stepwise logistic regression analysis, no statistically significant correlation was observed between Candida species count and other parameters such as age and gender of the patient, duration of DS, and frequency of treatment(s). ConclusionCUR-mediated PDT is an efficaciousness therapeutic modality for alleviating Candida species counts on the surface of denture and the palatal mucosa, as well as improving the salivary IL-6 and MMP-8 levels in DS patients.

Effects of Curcumin-mediated photodynamic therapy on autophagy and epithelial-mesenchymal transition of lung cancer cells

BackgroundThis study aimed to investigated whether Curcumin-mediated PDT can suppress EMT in lung cancer cells, and explore the roles of autophagy in the process of regulating EMT. MethodsLung cancer cell viability was assessed by CCK-8 assay. The expression of epithelial marker and mesenchymal markers, the conversion of LC3-I to LC3-II and the levels of p62 and beclin1 in A549 and SPCA1 cells were measured by Western blotting assay. The Wound healing and Transwell assays were used to detect the migration and invasion abilities of the A549 and SPCA1 cells. Autophagosome formation was detected via observing the colocalization of Lamp-2 with LC3 in A549 cells, and the autophagy ultrastructure was observed by TEM. ResultsCurcumin-PDT inhibited EMT, migration and invasion and induced autophagy in lung cancer cells. Curcumin-PDT induced autophagy was involved in the process of PDT inhibiting EMT, but it presented a promoting effect of EMT in lung cancer cells. Curcumin-PDT combined with CQ further inhibited EMT, invasion and migration of lung cancer cells. ConclusionsThe role of PDT-induced autophagy in the regulation of EMT was determined to be a promoting effect in lung cancer. Therefore, Curcumin-mediated PDT combined with autophagy inhibitor further suppressed EMT of lung cancer cells, and may represent a potential strategy against invasion and migration of lung cancer.

Curcumin-Mediated Photodynamic Therapy Inhibits the Phenotypic Transformation, Migration, and Foaming of Oxidized Low-Density Lipoprotein-Treated Vascular Smooth Muscle Cells by Promoting Autophagy: Erratum

Curcumin-Mediated Photodynamic Therapy Inhibits the Phenotypic Transformation, Migration, and Foaming of Oxidized Low-Density Lipoprotein-Treated Vascular Smooth Muscle Cells by Promoting Autophagy: Erratum

Curcumin-mediated Photodynamic Therapy Inhibits the Phenotypic Transformation, Migration, and Foaming of Oxidized Low-density Lipoprotein-treated Vascular Smooth Muscle Cells by Promoting Autophagy

Vascular smooth muscle cells (VSMCs) are becoming a hot spot and target of atherosclerosis research. This study aimed to observe the specific effects of curcumin (CUR)-mediated photodynamic therapy (CUR-PDT) on oxidized low-density lipoprotein (ox-LDL)-treated VSMCs and confirm whether these effects are mediated by autophagy. In this study, the mouse aortic smooth muscle cell line and A7r5 cell lines were used for parallel experiments. VSMC viability was evaluated by Cell Counting Kit-8 assay. VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro. The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting. The migration ability of the cells was detected by using transwell assay. The presence of intracellular lipid droplets was detected by Oil Red O staining. The results showed that VSMCs transformed from the contraction phenotype to the synthetic phenotype when stimulated by ox-LDL, during which autophagy was inhibited. However, CUR-PDT treatment significantly promoted the level of autophagy and inhibited the process of phenotypic transformation induced by ox-LDL. In addition, ox-LDL significantly promoted VSMC migration and increased the number of lipid droplets, whereas CUR-PDT treatment significantly reduced the ox-LDL-induced increase in the migration ability of, and lipid droplet numbers in, VSMCs. When the VSMCs were pretreated with the autophagy inhibitor 3-methyladenine for 24 hours, the effects of CUR-PDT were reversed. Therefore, our study indicated that CUR-PDT can inhibit the phenotypic transformation, migration, and foaming of ox-LDL-treated VSMCs by inducing autophagy.

Curcumin-loaded Pluronic® F-127 Micelles as a Drug Delivery System for Curcumin-mediated Photodynamic Therapy for Oral Application.

Antimicrobial photodynamic therapy (aPDT) is promising for oral decontamination. Curcumin has been used as photosensitizer; however, the hydrophobic properties can negatively affect aPDT. This study evaluated the aPDT efficacy using Cur-loaded Pluronic® F-127 micelles against Streptococcus mutans and Candida albicans biofilms. Micelles characterization was performed by zeta potential, dynamic light scattering, transmission electron microscopy, absorption and fluorescence spectroscopy. Cur concentrations, cell viability by CFUmL-1 and confocal microscopy were determined. Data were analyzed by parametric and nonparametric tests under 5%. Cur-loaded Pluronic® F-127 exhibited spherical shape, suitable particle size (≤100nm), adequate polydispersity index, best stability, lower photodegradation and autoaggregation compared to unloaded-Cur. Both microorganisms were sensitive to Cur-loaded Pluronic® F-127 micelles aPDT, with minimum inhibitory concentration (MIC) of 270μm and 2.1093μm for S.mutans and C.albicans suspended culture, respectively. Cur-loaded Pluronic® F-127 aPDT exhibited antibacterial/antifungal effect against the biofilms (~3 log10 reduction; P≤0.05); however, similar to unloaded (P≥0.05). Confocal images confirmed these results. Cur-loaded Pluronic® F-127 micelles exhibited good photo-chemical properties and may be a viable alternative to deliver Cur and to improve aPDT effect during the treatment of dental caries. Moreover, Pluronic® micelles can enhance the solubility, stability, permeability and control the release of Cur.

Influence of Oxidative Stress on Time-Resolved Oxygen Detection by [Ru(Phen)3]2+ In Vivo and In Vitro.

Detection of tissue and cell oxygenation is of high importance in fundamental biological and in many medical applications, particularly for monitoring dysfunction in the early stages of cancer. Measurements of the luminescence lifetimes of molecular probes offer a very promising and non-invasive approach to estimate tissue and cell oxygenation in vivo and in vitro. We optimized the evaluation of oxygen detection in vivo by [Ru(Phen)3]2+ in the chicken embryo chorioallantoic membrane model. Its luminescence lifetimes measured in the CAM were analyzed through hierarchical clustering. The detection of the tissue oxygenation at the oxidative stress conditions is still challenging. We applied simultaneous time-resolved recording of the mitochondrial probe MitoTrackerTM OrangeCMTMRos fluorescence and [Ru(Phen)3]2+ phosphorescence imaging in the intact cell without affecting the sensitivities of these molecular probes. [Ru(Phen)3]2+ was demonstrated to be suitable for in vitro detection of oxygen under various stress factors that mimic oxidative stress: other molecular sensors, H2O2, and curcumin-mediated photodynamic therapy in glioma cancer cells. Low phototoxicities of the molecular probes were finally observed. Our study offers a high potential for the application and generalization of tissue oxygenation as an innovative approach based on the similarities between interdependent biological influences. It is particularly suitable for therapeutic approaches targeting metabolic alterations as well as oxygen, glucose, or lipid deprivation.

The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats.

Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control-untreated; (ii) aPDT-treated with curcumin-mediated aPDT (blue light); (iii) artificial skin-treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin-treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm2) at the dose of 60 J/cm2 and the treatment with alcohol-based artificial skin was done with the topical application of 250 μL. Additional animals were submitted to aPDT combined with the artificial skin. After treatments, the number of colony-forming units (CFU) and the damage area were determined. Data were analyzed by two-way repeated measures ANOVA and Tukey tests. The highest reduction of the bacterial viability was observed in the PDT plus artificial skin group (4.14 log10), followed by artificial skin (2.38 log10) and PDT (2.22 log10) groups. In addition, all treated groups showed higher relative area of wound contraction (36.21% for the PDT, 38.41% for artificial skin, and 35.02% for PDT plus artificial) in comparison with the control group. These findings provide evidence for the positive benefits of aPDT with blue light and curcumin associated with artificial skin to decontaminate and accelerate the wound contraction.

Folate-Targeted Curcumin-Encapsulated Micellar Nanosystem for Chemotherapy and Curcumin-Mediated Photodynamic Therapy.

Curcumin (CUR) is a natural phenolic product used as a high-efficiency and low-toxicity anticancer drug and photosensitizer. However, it has a poor aqueous solubility and a lack of target specificity, which limits its clinical applications. Hence, we developed a folate-conjugated polymeric micelle to enhance the efficient delivery of CUR for effective cancer cell targeting and anticancer efficiency. A series of biocompatible folate-conjugated poly(2-(methacryloyloxy)ethylphosphoryl- choline)-b-poly(ε-caprolactone) (FPM) was synthesized with different hydrophobic lengths and folate contents. The prepared CUR-loaded micelles (CUR-FPM) possessed several superior properties, including an excellent drug loading capacity (6.3 ± 1.2%), improved CUR aqueous stability, fast-sustained CUR release in an acidic environment, and efficient intracellular production of reactive oxygen species. The in vitro cytotoxicity demonstrated that the CUR-FPM micelles efficiently suppressed the growth of HeLa cells (folate-receptor overexpression) compared to that of HT-29 cells, and a competition study showed less cytotoxic effect when free folic acid blocked the folate receptor, indicating the folate conjugation played the role of targeting the specific cells well. Moreover, the CUR-mediated photodynamic therapy (PDT) by CUR-FPM micelles under irradiation further inhibited the proliferation of cancer cells. All these results indicate that the CUR-FPM micelles could be a promising delivery system for folate-overexpressing cancer cells, complementary chemotherapy, and CUR-mediated photodynamic therapy.

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

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

Inactivation of microbes on fruit surfaces using photodynamic therapy and its influence on the postharvest shelf-life of fruits.

In this study, the disinfection effect of curcumin-mediated photodynamic therapy on the contact surfaces of fresh fruit was investigated. Our results showed that the optimum concentration of curcumin and the energy density required were 0.5 μM and 7.2 J/cm2, respectively. Photodynamic therapy showed an excellent disinfection rate for the fresh fruits with a reduction of more than 80% in the total bacteria and coliform counts. The photodynamic therapy inhibited species that belonged to the categories of gram-negative and facultative anaerobic bacteria, except for two species of the Trichoderma fungus. Importantly, photodynamic therapy prolonged the shelf-life of grapes for two days at room temperature. Therefore, photodynamic therapy should be commercialized as a high efficiency and non-thermal sterilization technology for use in the food industry.

Evaluation of curcumin-mediated photodynamic therapy on the reverse of multidrug resistance in tumor cells.

Curcumin (CUR) possesses photosensitive anti-tumor activity. However, photoactive CUR mainly targets tumor cells sensitive to chemotherapy, whereas the effect on multi-drug resistant cancer cells has not been fully investigated. The study aimed to investigate the anti-tumor activity of CUR on resistant MCF-7/ADM cells and its underlying mechanism providing insights into CUR-mediated PDT and a reference for reversing multidrug resistance. Cell apoptosis and morphological changes were detected by Annexin V-FITC/PI double staining and immunofluorescence, respectively. The apoptosis mechanism of CUR-mediated PDT was investigated by detecting the levels of reactive oxygen species (ROS), mitochondrial membrane potential, and related proteins. MTT and apoptosis results showed that CUR-mediated PDT significantly enhanced cytotoxicity and induced considerable cell apoptosis. After treatment with CUR-mediated PDT, cells became round in shape and shrunk, F-actin was loosely arranged, and the nucleus decreased in size. In addition, the level of ROS increased over time compared to the control and peaked at 6 h. CUR-mediated PDT induced alterations in the mitochondrial membrane potential, increased the release of mitochondrial cytochrome C (Cyt-c), and downregulated caspase-3/7/9, PARP, and P-gp. In conclusion, CUR-PDT induced apoptosis in resistant MCF-7/ADM cells primarily through endogenous mitochondrial apoptosis pathway. Besides apoptosis activation in resistant cells, the reverse of multidrug resistance was ascribed to the downregulation of P-gp expression to a degree.

Effect of curcumin-mediated photodynamic therapy on Streptococcus mutans and Candida albicans: A systematic review of in vitro studies.

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. 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. 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. 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.

Antifungal effect of photodynamic therapy mediated by curcumin on Candida albicans biofilms in vitro.

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. 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. 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). Curcumin-mediated PDT could effectively inactivateCandida albicans biofilms in vitro. Expression of genes involved in biofilms formation were downregulated after CUR-PDT.

Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo.

Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism.Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments.We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.

Curcumin-mediated Photodynamic Therapy for the treatment of oral infections-A review.

Recent evidences show the promising applications of Curcumin (CUR) against different diseases, including some of the main oral pathologies. The objective of this review paper was to catalog articles that investigated the photodynamic effect of CUR for oral diseases in the last 15 years. The establishment of defined criteria for data collection was proposed and a total of 173 articles were identified, but only 26 were eligible for full text reading. Their main findings were critically reviewed to provide a state-of-the-art overview of the use of CUR in Dentistry. Antimicrobial potential of CUR was the subject of the majority of the articles. CUR showed great potential for photodynamic action against oral bacteria, fungi, and strains resistant to conventional drugs. Some authors indicated the efficacy of CUR-mediated Photodynamic Therapy to reduce tumor cells while others observed low cytotoxicity in mammalian cells and healthy oral mucosa. However, CUR solubility and stability is still a problem for the photodynamic technique, and to overcome these drawbacks, biocompatible vehicles need to be better explored. Investigations have used different CUR concentrations and formulations, as well as different light parameters. This fact, together with the lack of in vivo studies, clearly shows that clinical protocols have not been established yet. Investigations are necessary in order to establish the best concentrations and safe vehicles to be used for this technique.

Effect of different pre-irradiation times on curcumin-mediated photodynamic therapy against planktonic cultures and biofilms of Candida spp

ObjectivesThe aim of this study was to evaluate the effects of pre-irradiation time (PIT) on curcumin (Cur)-mediated photodynamic therapy (PDT) against planktonic and biofilm cultures of reference strains of Candida albicans, Candida glabrata and Candida dubliniensis. Materials and methodsSuspensions and biofilms of Candida species were maintained in contact with different concentrations of Cur for time intervals of 1, 5, 10 and 20min before irradiation and LED (light emitting diode) activation. Additional samples were treated only with Cur, without illumination, or only with light, without Cur. Control samples received neither light nor Cur. After PDT, suspensions were plated on Sabouraud Dextrose Agar, while biofilm results were obtained using the XTT-salt reduction method. Confocal Laser Scanning Microscopy (CLSM) observations were performed to supply a better understanding of Cur penetration through the biofilms after 5 and 20min of contact with the cultures. ResultsDifferent PITs showed no statistical differences in Cur-mediated PDT of Candida spp. cell suspensions. There was complete inactivation of the three Candida species with the association of 20.0μM Cur after 5, 10 and 20min of PIT. Biofilm cultures showed significant reduction in cell viability after PDT. In general, the three Candida species evaluated in this study suffered higher reductions in cell viability with the association of 40.0μM Cur and 20min of PIT. Additionally, CLSM observations showed different intensities of fluorescence emissions after 5 and 20min of incubation. ConclusionPhotoinactivation of planktonic cultures was not PIT-dependent. PIT-dependence of the biofilm cultures differed among the species evaluated. Also, CLSM observations confirmed the need of higher time intervals for the Cur to penetrate biofilm structures.

Curcumin-mediated photodynamic inactivation ofCandida albicansin a murine model of oral candidiasis

In vitro investigations of curcumin-mediated photodynamic therapy (PDT) are encouraging, but there is a lack of reliable in vivo evidence of its efficacy. This study describes the photoinactivation of Candida albicans in a murine model of oral candidiasis, using curcumin as a photosensitizer. Forty immunosuppressed mice were orally inoculated with C. albicans and after five days, they received topical curcumin (20, 40 and 80 μM) and illumination with LED light. The use of curcumin or light alone were also investigated. Positive control animals did not receive any treatment and negative control animals were not inoculated with C. albicans. The number of surviving yeast cells was determined and analyzed by ANOVA and Tukey's post-hoc test (α = 0.05). Histological evaluation of the presence of yeast and inflammatory reaction was also conducted. All exposures to curcumin with LED light caused a significant reduction in C. albicans viability after PDT, but the use of 80 μM curcumin associated with light was able to induce the highest log10 reduction in colony counts (4 logs). It was concluded that curcumin-mediated PDT proved to be effective for in vivo inactivation of C. albicans without harming the host tissue of mice.

Phototoxic effect of curcumin on methicillin-resistant Staphylococcus aureus and L929 fibroblasts

Photodynamic therapy has been investigated as an alternative method of killing pathogens in response to the multiantibiotic resistance problem. This study evaluated the photodynamic effect of curcumin on methicillin-resistant Staphylococcus aureus (MRSA) compared to susceptible S. aureus (MSSA) and L929 fibroblasts. Suspensions of MSSA and MRSA were treated with different concentrations of curcumin and exposed to light-emitting diode (LED). Serial dilutions were obtained from each sample, and colony counts were quantified. For fibroblasts, the cell viability subsequent to the curcumin-mediated photodynamic therapy was evaluated using the MTT assay and morphological changes were assessed by SEM analysis. Curcumin concentrations ranging from 5.0 to 20.0 μM in combination with any tested LED fluences resulted in photokilling of MSSA. However, only the 20.0 μM concentration in combination with highest fluence resulted in photokilling of MRSA. This combination also promoted an 80% reduction in fibroblast cell metabolism and morphological changes were present, indicating that cell membrane was the main target of this phototherapy. The combination of curcumin with LED light caused photokilling of both S. aureus strains and may represent an alternative treatment for eradicating MRSA, responsible for significantly higher morbidity and mortality and increased healthcare costs in institutions and hospitals.