A study of the control of oral plaque biofilms via antibacterial photodynamic therapy

Aim: The aim of this study was to provide preliminary data on the most effective erythrosine concentration and light dose for the erythrosine-based photodynamic therapy (PDT) of oral plaque biofilms formed in vivo. Method: A randomized controlled study with 15 volunteers was carried out to investigate the effect of photosensitiser and light dose on the killing of bacteria in oral plaque biofilms formed in vivo. All volunteers wore a removable in situ appliance carrying 6 enamel slabs for two phases of two weeks each. During this time, plaque biofilms accumulated on the enamel slabs. The slabs were then removed from the appliances for PDT-treatment in vitro. In the first phase of the study, erythrosine doses of 22 and 220uM were used for the photodynamic treatment of the biofilms. In the second phase, the erythrosine concentration was kept constant, and the light dose was varied. Following treatment, the biofilms were disaggregated, and the total bacterial killing determined using colony counting. Results: The erythrosine dose of 220uM caused the most cell killing relative to controls. Fifteen minutes continuous irradiation with light and light fractionation of 5x1 minute irradiation separated by 2 minute dark recovery periods were found to be the most effective bactericidal regimes. Conclusion: Erythrosine-based PDT shows promise as an anti-bacterial treatment for oral plaque biofilms. Further research is needed to prove its clinical and cost-effectiveness compared with current best practice

Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans

Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/13313–9

In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers

10.1038/nm.2933Nature Medicine18101580-1585NAME

Spray-Dried Microparticles Containing Polymeric Micelles Encapsulating Hematoporphyrin

The purpose of this study was to examine the properties of a new pulmonary delivery platform of microparticles containing micelles in which a therapeutic photosensitizing drug, hematoporphyrin (Hp), was encapsulated. Different poloxamers were used to form micellar Hp, and one of these, Pluronic L122-Hp, was subsequently incorporated into lactose microparticles by spray-drying. Spectral and morphological analyses were performed on both micellar Hp, and lactose microparticles containing micellar Hp (lactose-micellar Hp) before and after dissolution of the microparticles in water. Photodynamic activity of the various Hp samples were evaluated in human lung epithelial carcinoma A549 cells using a light-emitting diode (LED) device at a wavelength of 630 ± 5 nm. No significant difference was observed between micellar Hp and lactose-micellar Hp regarding the generation of singlet oxygen. The mean particle size of the microparticles was 2.3 ± 0.7 µm which is within the size range for potential lung delivery. The cellular uptake of micellar Hp and lactose-micellar Hp measured on A549 cells was at least twofold higher than those obtained with the Hp at equivalent concentrations. Micellar Hp exhibited higher cytotoxicity than Hp due to reduced formation of Hp aggregates and increased cellar uptake. The spectral properties as well as the photodynamic activity of the micellar Hp was retained when formulated into microparticles by spray-drying. Microparticles containing micelles have the potential for delivering micelle-encapsulated hydrophobic drugs in targeted therapy of pulmonary diseases

Interactions of amino acids with aluminum octacarboxyphthalocyanine hydroxide. Experimental and DFT studies

The influence of albumin and amino acids (l-serine, glycine, l-histidine, l-tryptophan, l-cysteine) on the properties of aluminum octacarboxyphthalocyanine hydroxide (Al(OH)PcOC) was investigated in a phosphate buffer (pH 8.0). Particular attention was paid to the spectroscopic properties and photostability of Al(OH)PcOC. The effect of albumin or amino acids on the photodegradation of Al(OH)PcOC was examined in water using red light: 685 nm and daylight irradiation. Analysis of kinetic curves indicated that interaction with those molecules increases the photostability of Al(OH)PcOC. The molecular structure of Al(OH)PcOC complexes (in vacuum and in water) with axially or equatorially coordinated amino acids was studied by the B3LYP/6-31G* method, and the effects on molecular structure and electronic absorption spectrum were investigated on the basis of the density functional theory. The calculation results revealed that axial coordination significantly reduces the non-planarity of the phthalocyanine ring, and, thus, alters the electronic structure. On the other hand, hydrogen bonding of phthalocyanine side COOH groups with amino acids, in equatorial complexes, does not change the structure within the center of the phthalocyanine, and causes only a slight increase in UV–vis bands intensity, which is in perfect agreement with experimental data. [Figure not available: see fulltext.