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.

Design and Characterization of Mucoadhesive Gelatin-Ethylcellulose Microparticles for the Delivery of Curcumin to the Bladder.

BACKGROUND: Bladder cancer is the second type of malignant carcinoma of the urinary tract. The treatment is time-consuming and requires maintenance doses of the drug for long period of time with important side effects. Curcumin has shown evident clinical advances in the treatment of cancer. The technology of microencapsulation and the use of mucoadhesive materials can contribute to modify the delivery and improve the bioavailability of curcumin. OBJECTIVE: The aim of this study was to design and characterize mucoadhesive microparticles containing curcumin using multivariate analysis and the spray-drying technique. METHODS: A factorial design 32+1 was employed to investigate the influence of gelatin, ethylcellulose, and curcumin on size, polydispersity index, drug content and entrapment efficiency. Microparticles were also evaluated by ATR-FTIR, X-ray diffraction, antioxidant activity, in-vitro release profile, exvivo mucoadhesion performance, and in-vitro cytotoxicity. RESULTS: Microparticles showed non-uniform surface, mean diameter from 2.73 µm to 4.62 µm and polydispersity index from 0.72 to 1.09, according to the different combinations of the independent factors. These independent variables also had a significant effect on the drug content. The highest values of drug trapping efficiency were obtained with the highest concentration of curcumin and polymers. Formulations displayed slow drug release and important antioxidant activity. The good mucoadhesive performance of microparticles was assessed by the falling film technique. Moreover, the formulations did not display in vitro toxicity against Artemia salina and Fibroblasts LM(TK). CONCLUSION: The design results were useful for developing of curcumin dosage form with good physicochemical characteristics and mucoadhesive properties for the bladder administration.

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.

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.

Perfil epidemiológico do câncer infantil em população atendida por / Epidemiological profile of childhood cancer in population attended for a pediatric

O câncer na infância é um evento raro, que representa cerca de 1 por cento das neoplasias diagnosticadas nos países em desenvolvimento. O planejamento de medidas preventivas requer estudos epidemiológicos em diferentes áreas geográficas, os quais ainda são insuficientes para a definição de ocorrência, distribuição e fatores de risco da doença. Este trabalho descreve o perfil epidemiológico do câncer infantil em uma unidade de oncologia pediátrica de Salvador. Foram tomados para o estudo os prontuários dos pacientes admitidos na instituição no período de 1995 a 2003. Dos 465 pacientes estudados, 57,8 por cento eram do sexo masculino, 50,8 por cento eram pardos e 40,1 por cento eram naturais da Região Metropolitana de Salvador. Os tipos de câncer mais freqüentes foram as leucemiùs, seguidas pelos linfomas e osteossarcomas, 39,5 po cento, 18,9 por cento e 9,9 por cento respectivamente. Como principais causas de óbito, destacaram-se, em ordem decrescente: leucemias, osteossarcomas, linfomas e neuroblastoma. A sobrevida global livre de doença no período representou 51 por cento da população estudada, o número de óbitos 38,3 por cento e o número de abandonos de tratamento, 2,4 por cento. Em 21 por cento dos casos, havia relatos de outros casos de câncer na família e em 4 por cento foi registrada exposição anterior a algum tipo de agente reconhecidamente tóxico. No entanto, a análise de possíveis fatores de risco associados ao desenvolvimento de neoplasias foi prejudicada emvirtude da falta de registro desses aspectos na maioria dos prontuários analisados. São necessários novos estudos sobre o tema, que possam contribuir para a epidemiologia do câncer infantil e associar possíveis fatores de risco em áreas geográficas específicas.