Impact of light-activated curcumin and curcuminoids films for catheters decontamination.

BACKGROUND: Biofilms are microbial communities protected by an extra polymeric matrix, which promotes a defense against antimicrobial agents. Cells attached in surfaces and promote infections. Photodynamic inactivation (PDI) is one of the strategies to eliminate infections due to the facility of use and the absence of resistance by bacteria. The study combines formulation with curcuminoids and with Photogem(R), illuminating them with 450 nm and 630 nm, respectively. METHODS: Films were prepared with pectin, glycerin, Sodium Lauryl Sulfate, curcumin, curcuminoids, or Photogem(R) (0.75; 0.75 mg/mL and 0.03 mg/mL respectively). Bacterial biofilms were formed during 3, 4, or 7 days on catheters and illumination with LED devices at 450 nm and 630 nm. RESULTS: The best PDI applied in S. aureus 7-days biofilm with curcuminoid film. Photogem film was the best strategy for PDI in E. coli 7-day biofilm. Curcumin film promoted similar results with S. aureus and E. coli. Light penetration demonstrated a similar decreased exponential curve along the increase of thickness of biofilm. CONCLUSION: Curcuminoids, curcumin and Photogem® show efficient solubilization and availability in formulation with relevant results in PDI. S aureus biofilms were more susceptible to curcuminoid film. E coli biofilms were more susceptible to Photogem film.

Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action.

Hospital-acquired infections are a global health problem that threatens patients' treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient's trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT's functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy's potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

Antibacterial Photodynamic Inactivation of Antibiotic-Resistant Bacteria and Biofilms with Nanomolar Photosensitizer Concentrations.

Gram-negative bacteria and bacteria in biofilms are very difficult to eradicate and are 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 that are 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 the efficacy of inactivation. We demonstrate the relevance of size for drug diffusion in biofilms. The 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.

Photodynamic Therapy Versus Glucose for the Treatment of Telangiectasia: A Randomised Controlled Study in a Rabbit Ear Model.

OBJECTIVES: Telangiectasia is a common venous formation that mainly affects women and causes discomfort, including psychological distress. This study compared photodynamic therapy (PDT) with glucose for vessel sclerosis in a rabbit ear model. METHODS: Thirty-six ears of 18 rabbits were randomly divided into four groups: Group 1: only injection of Photogem (4 mg/mL); Group 2: only light (635 nm, 100 mW/cm2, 8 min, 48 J/cm2); Group 3: glucose 75% injection; Group 4: PDT procedure with injection of Photogem and illumination immediately after. Injections were made into the central ear artery. After injection or sham procedures, manual compression of the marginal vein was maintained for 8 min in all ears. Follow up was immediately after the procedures, and one and six days later. The percentage of length reduction of spider veins, the target vessels, was analysed in digital photographs with Image J software. Ear thermographs were made with a thermocamera device and average temperatures were collected for analysis. Ear biopsies were obtained after six days. Endothelium average, inflammation, fibrosis, necrosis, skin burn, and vascular thrombosis were assessed using a specific score. RESULTS: The mean vessel length reduction was 26% for Group 4, 2.4% for Group 3, .4% for Group 1, and 0 for Group 2, highlighting that in Group 4, the vessel lengths were significantly reduced compared with the other groups (p < .001). In the thermal analysis, in Group 3, the temperature was unchanged from the initial temperature and the central diameter vessel increased after six days, while, in Group 4, the temperature decreased and the vessels were not clearly detected, suggesting a reduction of the vessels and smaller infusion. Histology showed no difference among groups and one case of necrosis was found in Group 4. CONCLUSIONS: PDT was associated with significantly more target vessel sclerosis than glucose injection and controls.

Acceleration of newborn rats' development with the use of photobiomodulation and the near possibility of application in human premature babies.

Photobiomodulation was explored to find evidence of stimulation during the development of newborn rats. A light chamber device was used, and rat pups were divided into groups after birth. Investigation of the process' security was performed before the full experiment. Following a protocol of alternating illumination and mother's presence during the first 13 days, we observed that, in the group that received photobiomodulation, the pups opened their eyes faster, indicating earlier achievement of maturity. The rate of weight gain also indicates faster metabolic activity in the group that was photostimulated. This study is the first step toward the use of photobiomodulation for premature newborn human babies.

Biofilm Destruction on Endotracheal Tubes by Photodynamic Inactivation.

BACKGROUND: Hospital infections are a public health problem that can occur with the use of catheters and endotracheal tubes (ETT). Pathogenic microorganisms may adhere to surfaces of these materials forming a biofilm and produce an extracellular polymer matrix that promotes resistance of microorganisms to factors such as pH, temperature and drugs. The conventional treatment is being made by antibiotics, which has serious adverse effects in immunocompromised patients. Photodynamic therapy (PDT) is an alternative for microbial inactivation noninvasive without the stimulus of microbial resistance. PDT combines light and a photosensitive molecule for produce reactive oxygen species leading to bacterial death. OBJECTIVE: The objective of this study was to determine the efficacy of a PDT protocol in bacterial inactivation of biofilm ETT. METHOD: The photosensitizer (PS) used was curcumin and the light source LED at 450nm. A statistical experimental design was used for optimization of antimicrobial PDT. RESULTS: The highest microbial inactivation was observed with 70% biofilm reduction in conditions 1.25 mg/mL curcumin, 2 h of PS incubation and 50 J/cm2. CONCLUSION: This study described the photodynamic death of bacteria forming a biofilm on ETT. Parameters optimization was important for clinical application of this system.

Photostimulation effects on chicken egg development: Perspectives on human newborn treatment.

It is well known that, under exposure to bright light, eggs tend to hatch earlier than control, without any damage to the birds. This report aims to systematically show the effect and establishes a proposal for a possible application to accelerate chicken egg formation, which could be extrapolated or adapted as a great advance in premature human newborns. Comparing several protocols, the experiments show that lower doses of light slowly delivered for 24 h promote higher efficiency in embryo development, increasing on average 25% of its size and more than 70% in weight when compared to the control. This weight difference shows promising results compared to rates of up to 17% found in the literature. These results can be a first step to reduce the stay of premature human infants in hospitals because light, when applied in very low doses, can accelerate the natural biological processes without risks.

Fluorescence analysis of a tumor model in the chorioallantoic membrane used for the evaluation of different photosensitizers for photodynamic therapy.

The development of a tumor in the chicken chorioallantoic membrane (CAM) enables a more individualized understanding of the dynamics of the photosensitizer (PS) interaction with the tumor blood vessels and cells. Photogem® and 5-aminolevulinic acid (ALA), a protoporphyrin IX (PpIX) precursor, were used as PS and their red fluorescence enabled the monitoring of PS dynamic distribution in the vessels and in the tumor. With a tumor model in CAM and fluorescence assessment, the aim of this study was to evaluate the PDT parameters comparing different photosensitezers. In this model, the topical application was chosen as the best way of drug delivery and widefield fluorescence images were at every 30min. The images were processed in a MATLAB® routine for a semi-quantitative analysis of the red fluorescence. PpIX formation in the blood vessels and in the tumor region was observed after 3h and 1.5h, respectively, whereas Photogem® was accumulated in the tumor region after 2h. The illumination was performed by a diode laser with emission centered at 635nm and irradiance of 80mW/cm2 for 10min. After PDT irradiation, the photobleaching for both compounds was observed. Photogem® showed a reduced photobleaching, however, both PS induced a destruction of the tumor mass and vascular network in the treated area.