Screening and In Vitro Evaluation of Mucoadhesive Thermoresponsive System Containing Methylene Blue for Local Photodynamic Therapy of Colorectal Cancer.

PURPOSE: Photodynamic therapy (PDT) with methylene blue (MB) constitutes a potentially useful modality for colorectal cancer treatment. The limitations of the formulations containing MB are problems of administration and the inability to get the closeness contact at the site during the appropriate residence time. Present study aimed to develop and characterize mucoadhesive thermoresponsive system containing MB designed as platform for colorectal cancer therapy. METHODS: Formulations composed of different amounts of poloxamer 407 (Polox), Carbopol 934P (Carb), and MB were developed and characterized as rheological, compressional, mucoadhesive and syringeability properties, toxicity, photodynamic action, in vitro MB release profile, and ex vivo MB intestinal permeation. RESULTS: The different compositions resulted in formulations with distinctive macroscopic characteristics and wide range of gelation temperatures. The compressional flow, mucoadhesive, syringeability, and rheological properties were significantly influenced by temperature and/or composition. The MB release from formulation was governed by anomalous transport. In addition, it was observed that MB permeated the intestinal membrane; the formulation possesses photodynamic activity and low toxicity. CONCLUSIONS: The data obtained from the system composed of 20% Polox, 0.15% Carb, and 0.25% MB indicated a potentially functional role in PDT of the colorectal cancer and suggest it is worthy of clinical evaluation.

Response surface method optimization of a novel Hypericin formulation in P123 micelles for colorectal cancer and antimicrobial photodynamic therapy.

The photodynamic properties of Hypericin (Hyp) may be used as an alternative treatment for malignancies of the lower gastrointestinal tract and for the prevention of surgical-site infection; however, its use in photodynamic therapy has been limited because of its poor hydrosolubility. Therefore, in order to improve its water solubility and its photodynamic effect, Hyp was encapsulated in Pluronic P123 (P123) and the photodynamic effects against intestinal and epidermal bacteria and against two lineages of intestinal colon carcinoma cells were investigated. Two response surface methods (RSM) were used to achieve the best in vitro photodynamic activity against Enterococcus faecalis, Escherichia coli and Staphylococcus aureus: in the first (full 23 RSM), Hyp concentration (HC*), incubation time (IT*) and LED-light time (LT*) were considered as the independent variables and E. faecalis inhibition as the dependent variable. In the second (full 32 RSM), Hyp concentration (HC*) and P123 concentration (CC*) were considered as independent variables and E. faecalis, E. coli and S. aureus inhibition as dependent variables. The optimized experimental conditions achieved were: Hyp concentration=37.5µmol/L; P123 concentration=21.5 µmol/L and 6.3J/cm2, which resulted in 2.86±0.12 and 2.30±0.31CFU log-reductions of E. faecalis and S. aureus. No effect was seen against E. coli. The cytotoxic effects of Hyp/P123 were also investigated for Caco-2 and HT-29 intestinal colon carcinoma cells at Hyp/P123 concentrations of 1, 0.5, 0.25 and 0.1µmol/L for Caco-2 cells and 4, 3, 2 and 1µmol/L for HT-29 cells. The cytotoxic concentrations for 50% (CC50) and 90% (CC90) of Hyp/P123 were 0.443 and 0.870µmol/L for Caco-2 cells and 1.4 and 2.84µmol/L for HT-29 cells. The P123 nanocarrier played a significant role in the permeation of Hyp through the cell membrane leading to significant cell death, and showed itself to be a promising photosensitizer for PDT that could be suitable for the treatment of colonic diseases since it is effective against positive Gram bacteria and intestinal colon carcinoma cells.

Preparation and characterization of bioadhesive system containing hypericin for local photodynamic therapy.

Hypericin (Hyp) is a natural photoactive pigment utilized in the treatment of different types of cancer and antimicrobial inactivation using photodynamic therapy (PDT). Hyp is poorly soluble in water leading to problems of administration, getting close contact with the site, and bio-availability. Therefore, this study aimed to develop bioadhesive thermoresponsive system containing Hyp for local PDT. Carbomer 934P, poloxamer 407, and Hyp were used to prepare the thermoresponsive bioadhesive formulations. They were characterized for sol-gel transition temperature, mechanical, mucoadhesive, rheological (continuous flow and oscillatory) and dielectric properties, syringeability, in vitro Hyp release kinetics, ex vivo permeability, and photodynamic activity. The formulations displayed suitable gelation temperature and rheological characteristics. The compressional, mechanical and mucoadhesive properties, as well the syringeability showed the easiness of administration and the permanence of the system adhered to the mucosa or skin. The dielectric analysis helped to understand the Hyp availability, and its release presented an anomalous behavior. The system did not permeate the pig skin nor rat intestine and showed good biological photodynamic activity. Therefore, data obtained from the bioadhesive system indicate a potentially useful role as a platform for local hypericin delivery in PDT, suggesting it is worthy of in vivo evaluation.

Observações sobre a epidemiologia e o nível de conhecimento da Leishmaniose Tegumentar Americana, em região endêmica no sul do Brasil / Observations about epidemiology and awareness of American Tegumentary Leishmaniasis in endemic region in southern Brazil

Foi realizado um inquérito com famílias residentes em área endêmica (Bairro Inocente Vila Nova Júnior, Maringá ­ Paraná), que tiveram histórico de Leishmaniose Tegumentar Americana, visando identificar o nível de conhecimento e a prevalência da infecção. Das 28 pessoas entrevistadas, 23 tiveram a doença e 05 tiveram mais de um caso na família, totalizando 36 indivíduos que apresentaram a doença, no período de 2001 a 2010. Na região estudada observa-se a presença de uma mata residual, que propicia o desenvolvimento do vetor, 100% (28) dos entrevistados afirmaram a presença de flebotomíneos nas residências, porém apenas 67% disseram adotar medidas preventivas contra esses. Pôde-se notar que o conhecimento a cerca da doença limita-se a quem já teve algum contato com ela, e mesmo desconhecendo as peculiaridades da infecção, a conduta de 100% das pessoas é procurar o serviço médico. Nota-se que a falta de entendimento epidemiológico, é um importante obstáculo na criação de campanhas preventivas eficazes, o que impossibilita a diminuição da incidência.

A survey was conducted with families living in endemic areas (neighborhood Inocente Vila Nova Junior, Maringá - Paraná), who had history of leishmaniasis, to identify the knowledge level and the prevalence of infection. Of the 28 people interviewed, 23 had the disease and 5 had more than one case in the family, totaling 36 individuals who had the disease in the period 2001 to 2010. In the area where the cases occurred is the presence of a residual forest, which enables the vector's development, 100% (28) of respondents said that they saw sandflies presence in homes, but only 67% said they had used preventative measures against them. It might be noted that the knowledge about the disease is confined to those who had any contact with its, and even ignoring the peculiarities of the infection, conduct 100% of the people is to seek medical attention. We could note that the lack of understanding of epidemiology, is a major obstacle in creating effective prevention campaigns, which prevents a decrease in the incidence.