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.

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.