Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy

Abstract

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.

Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates

“…The capacity of MB as a light-driven 1 O 2 generator has been widely utilized in a number of studies 45, 46 . Under the irradiation of red light (λ max  = 666 nm), MB monomers produce 1 O 2 through the type II photochemical pathway, in which the energy from triplet state MB (i.e., 3 MB + ) is transferred to molecular oxygen 20 , and the generated 1 O 2 oxidizes organic compounds nearby 47 .…”

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

“…Recently, in order to improve the uptake of PS by microorganisms during PDT approach, these molecules has been loaded, linked or encapsulated in a drug delivery system for widely different purposes [57, 58]. …”

“…Junqueira et al [57] demonstrated that the utilization of functional polymeric systems composed of poloxamer 407, Carbopol 934P, and MB have a good capability for singlet oxygen generation in PDT. They demonstrated the formulation of a system with a suitable gelation temperature and good MB release, intended to be applied on the skin and/or oral mucous membranes.…”

Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems: structural, rheological, mechanical, textural, and bioadhesive characterization and evaluation of in vivo anti-inflammatory activity

“…In addition, after formulation application, ie, when the force application ceases, the formulation has the ability to recover its initial high viscosity, and thus it remains at the site of action for a longer time. 55 As such, the addition of cosurfactants, salts, or other components, such as drugs, may influence the characteristics of LC mesophases, such as viscosity, via interference with the electrostatic interactions or chemical bonds between components of the formulation. [56][57][58] It is noteworthy that the incorporation of Res decreased the consistency index (k) of all formulations, which demonstrated that this drug affected molecular bonds between formulation components, resulting in a decrease in viscosity.…”