Abstract
Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant Staphylococcus aureus, (MRSA), Escherichia coli, and Pseudomonas aeruginosa. This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species in vitro and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing in vivo of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability in vitro, with a minimum inhibitory concentration of 15.6 μM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 μM against MRSA and E. coli and 62.5 μM against P. aeruginosa. In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED–aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED–aPDT has a promising bactericidal effect both in vitro and in vivo, and PPIX-MED–aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.
Highlights
Antimicrobial drugs are overused, misused, and widely applied prophylactically, which results in the emergence of drugresistant microorganisms (Park et al, 2012)
The principal aim of this study was to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) in vivo on healing of experimental rat burn wounds infected with a mixture of pathogenic bacteria
protoporphyrin IX (PPIX)-MED is a photosensitizer with relatively high photostability
Summary
Antimicrobial drugs are overused, misused, and widely applied prophylactically, which results in the emergence of drugresistant microorganisms (Park et al, 2012). Multidrug-resistant bacterial infections are a major challenge to healthcare and an important cause of morbidity and mortality in hospitalized patients (Hamblin et al, 2002; Oda et al, 2004; Davies and Davies, 2010; Jernigan et al, 2020). Burning causes a rupture in the skin and other epithelial layers, which exposes the individual to infection as open wounds allow bacteria to enter and are suitable environments for their survival (Oyama et al, 2020). A delay or failure in the treatment of wounds can lead to progressive bacterial colonization until the development of a systemic infection (Oyama et al, 2020). Anti-infection treatment is important for burn patients (Mai et al, 2017)
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