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Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future.

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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.

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This study describes the investigation about the physicochemical behavior of methylene blue (Mb) addition to systems containing poloxamer 407 (Polox), Carbopol 934P (Carb), intended to be locally used by photodynamic therapy. A factorial design 2 (plus center point) was used to analyze the rheological, mucoadhesive and textural properties of the preparations. Systems containing the lower concentrations of Polox (15 and 17.5%, w/w) exhibited pseudoplastic flow and low degrees of rheopexy. On the other hand, at higher Polox concentration (20%, w/w) the systems display plastic flow and thixotropy. Carb and Mb exhibited a negative influence for the consistency and flow behavior index, due to the interaction between them. For most of the formulations, the increase of Polox and Mb content significantly increased storage modulus, loss modulus and dynamic viscosity. The systems display a sol-gel transition temperature, existing as a liquid at room temperature and gel at 29-37 °C. Increasing the temperature and the polymer concentration, the compressional properties of systems significantly increased. The mucoadhesion was noted to all formulations, except to systems composed by 15% (w/w) of Polox. The analyses enabled to understand and predict the performance of formulations and the polymer-Mb interactions, tailoring to the suit systems (Polox/Carb/Mb): 17.5/0.50/0.20 and 20/0.15/0.25.

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