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Innovative strategies to eliminate bacterial biofilms: optimization of antimicrobial photodynamic therapy

Grant number: 18/15660-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Effective date (End): October 31, 2021
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Mauricio da Silva Baptista
Grantee:Laura Marise de Freitas
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The costs associated with chronic skin wounds reach $25 billion per year in the United States alone. With the increasing incidence of conditions that contribute negatively to wound healing, especially obesity and diabetes, this burden tends to increase exponentially. The biggest challenge in the healing process of these wounds is bacterial infection, which establishes itself in the form of biofilms and contributes to the chronic process. The extracellular matrix of the biofilm prevents phagocytosis, and binds to antimicrobial agents, blocking its diffusion or preventing its action. These characteristics make the resolution of these infections difficult to achieve by conventional antimicrobial methods. Alternative therapies have been investigated, including antimicrobial photodynamic therapy (aPDT). With its mechanism of action based on the generation of reactive oxygen species after the activation of a photosensitizer (PS) by light, aPDT causes death quickly and independently of specific metabolic pathways. However, as with other drugs, the PS has its penetration in the polymeric matrix of the biofilm impaired, reducing the effectiveness of the therapy. Developing pharmaceutical vehicles that can contribute to microbicidal activity, while facilitating the penetration of the PS into biofilm, is the key to achieve the full therapeutic potential of aPDT. In this context, this project aims to explore molecular and physicochemical approaches that result in the disassembling of the extracellular matrix of the biofilm and consequent optimization of the aPDT, culminating in the development of a nanostructured system for the administration of the PS methylene blue, aimed at the treatment of chronic skin infections. This system should improve the efficacy of aPDT and reduce the time of treatment, benefiting the quality of life of patients, and avoid the use of systemic antibiotics, minimizing the emergence of new resistant variants.