Adjaci Uchoa Fernandes

Protoporphyrin IX Nanoparticle Carrier: Preparation, Optical Properties, and Singlet Oxygen Generation

The present study is focused on developing a nanoparticle carrier for the photosensitizer protoporphyrin IX for use in photodynamic therapy. The entrapment of protoporphyrin IX (Pp IX) in silica spheres was achieved by modification of Pp IX molecules with an organosilane reagent. The immobilized drug preserved its optical properties and the capacity to generate singlet oxygen, which was detected by a direct method from its characteristic phosphorescence decay curve at near-infrared and by a chemical method using 1,3-diphenylisobenzofuran to trap singlet oxygen. The lifetime of singlet oxygen when a suspension of Pp IX-loaded particles in acetonitrile was excited at 532 nm was determined as 52 micros, which is in good agreement with the value determined for methylene blue in acetonitrile solution under the same conditions. The Pp IX-loaded silica particles have an efficiency of singlet oxygen generation (eta Delta) higher than the quantum yield of free porphyrins. This high efficiency of singlet oxygen generation was attributed to changes on the monomer-dimer equilibrium after photosentisizer immobilization.

Synthesis of Phthalocyanines−ALA Conjugates: Water-Soluble Compounds with Low Aggregation

Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic acid (ALA) linked to the core structure are described. These compounds were prepared by using original functionalizations, and they present remarkable structural and photophysical features, indicating that they could be applied to photodynamic therapy (PDT).

Photo-activated phase separation in giant vesicles made from different lipid mixtures

Using giant unilamellar vesicles (GUVs) made from POPC, DPPC, cholesterol and a small amount of a porphyrin-based photosensitizer that we name PE-porph, we investigated the response of the lipid bilayer under visible light, focusing in the formation of domains during the lipid oxidation induced by singlet oxygen. This reactive species is generated by light excitation of PE-porf in the vicinity of the membrane, and thus promotes formation of hydroperoxides when unsaturated lipids and cholesterol are present. Using optical microscopy we determined the lipid compositions under which GUVs initially in the homogeneous phase displayed Lo-Ld phase separation following irradiation. Such an effect is attributed to the in situ formation of both hydroperoxized POPC and cholesterol. The boundary line separating homogeneous Lo phase and phase coexistence regions in the phase diagram is displaced vertically towards the higher cholesterol content in respect to ternary diagram of POPC:DPPC:cholesterol mixtures in the absence of oxidized species. Phase separated domains emerge from sub-micrometer initial sizes to evolve over hours into large Lo-Ld domains completely separated in the lipid membrane. This study provides not only a new tool to explore the kinetics of domain formation in mixtures of lipid membranes, but may also have implications in biological signaling of redox misbalance.

The synthesis of a water-soluble derivative of rutin as an antiradical agent

The purpose of this study was to synthesize a water-soluble derivative of rutin (compound 2) by introducing carboxylate groups on rutins sugar moiety. The rutin derivative showed an almost 100-fold solubility increase in water. The antiradical capacity of compound 2 was evaluated using the luminol/AAPH system, and the derivatives activity was 1.5 times greater than that of Trolox®. Despite the derivatives high solubility in water (log P = -1.13), lipid peroxidation of brain homogenate membranes was very efficiently inhibited (inhibition values were only 19% lower than the inhibition values of rutin).

Antioxidant activity, cito- and phototoxicity of pomegranate (Punica granatum L.) seed pulp extract

Neste trabalho, foi realizada a extracao de sementes inteiras de roma (Punica granatum L. - Punicaceae) com cachaca durante 80 horas no escuro. A curva de dessorcao do extrato apresentou um tempo otimo de extracao das sementes de aproximadamente 24 horas. O extrato obtido foi dividido em duas amostras, uma delas foi mantida protegida da luz ambiente (extrato 1) e a outra nao (extrato 2). As amostras foram caracterizadas por espectroscopia Ultravioleta-Visivel, quantificacao de polifenois totais pelo metodo de Folin-Ciocalteu e pela atividade antioxidante utilizando o ensaio de inibicao do radical DPPH. A exposicao do extrato a luz ambiente, o fez perder 9,8% do seu teor de polifenois totais (de 0,353 para 0,322 g.L-1). Por outro lado, a atividade antioxidante caiu a 20,7% (de 3,4 para 0,7 mM de trolox). A adicao de ate 3% do extrato 1 de sementes de roma nao afetou significativamente a viabilidade de celulas epiteliais in vitro. As mesmas celulas tratadas com o extrato 1 e irradiadas com um simulador solar nao apresentaram fototoxicidade na mesma faixa de concentracao. Assim, foi possivel concluir que os componentes das sementes de Punica granatum L. (roma) podem ser extraidos por contato direto com cachaca por um periodo de 80 horas no escuro, conferindo-lhe uma boa coloracao e tambem propriedades organolepticas agradaveis. Tal extrato nao apresenta citotoxicidade e nem fototoxicidade, embora o extrato tenha se mostrado fotoinstavel.

Photophysical properties of porphyrin derivatives: Influence of the alkyl chains in homogeneous and micro-heterogeneous systems

This work is focused on the evaluation of the photophysical properties of protoporphyrin-IX derivatives with different alkyl chains. The goal of this work is to understand the physicochemical properties and select prototypes of photosensitizers for photodynamic therapy. Solvents with different dielectric constants were used to obtain relevant data on different physical and chemical processes, such as fluorescence quantum yield and emission level of aggregation in nonpolar media. In addition, studies were conducted in micro-heterogeneous systems through the interaction of porphyrin derivatives with different surfactants, such as cetyltrimethylammonium bromide, sodium dodecyl sulfate and octyl phenol ethoxylate. The compounds were characterized by electronic absorption spectroscopy in the ultraviolet-visible region and fluorescence emission spectroscopy. The comparative study between the different chemical environments evaluated in the present study represents a relevant contribution to the comprehension of the properties acquired by the porphyrins in different micro-heterogeneous systems, which allows us to understand various interactions that these compounds are subject in biological medium, such as the influence of the polarity of the medium in the reactivity of porphyrins with nonpolar substituents. These results show the decisive physicochemical influence of the alkyl chains on the properties of the tetraazomacrocycle porphyrin.

Chlorophyllin-M: A new substance for photodynamic therapy in the retina and choroid.

Chlorophyllin‐M is a new chlorophyll‐based derivative photosensitive compound developed by our research group with easy laboratorial synthesis and ideal properties for photodynamic therapy (PDT). It is intended for clinical treatments with simple and low cost techniques and reagents. The objective of this study is to evaluate if intravenous chlorophyllin‐M is able to deliver a photosensitizer to rabbit retina and rabbit choroid and promote PDT after ocular irradiation with a 660 nm LASER.

Application of photodynamic therapy with led and methylene blue in streptococcus mutans in the presence of glucose- in vitro study

BASIC SCIENCE AND TRANSLATIONAL RESEARCH

Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum

BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring.