Antimicrobial Photodynamic Therapy Combined With Antibiotic in the Treatment of Rats With Third-Degree Burns

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.

Photodynamic Therapy of Novel Photosensitizer Ameliorates TNBS-Induced Ulcerative Colitis via Inhibition of AOC1

“…Our previous research has shown that LD 4 could inactivate microbial pathogens in traumatic infection (( Meng et al, 2015 ; Xu et al, 2016 ; Zhao et al, 2021 ). We have proved that the three different doses of LD 4 used in this paper have no significant effect on normal rats and PDT alone did not significantly relieve UC ( Supplementary Figure S1F,G ).…”

“…Cells were cultured with LD 4 for 30 min. The time was sufficient for bacteria to take up LD 4 , as demonstrated in the bacterial strain deactivation previously reported ( Xu et al, 2016 ; Zhao et al, 2021 ), so we chose this time to investigate the cellular damage occurring under the same conditions. Cells were irradiated with an energy density of 6 J/cm 2 or kept in the dark for 30 min, following which the cells were cultured for a further 24 h before MTT assay.…”

“…We designed and synthesized a series of alkaline amino acid modified amino tetraphenyl porphyrin compounds, all of which showed good physical and chemical properties ( Meng et al, 2015 ). One of the compounds, 5,10,15,20-tetra{4-[(S)-2,6-diamino-hexamide] phenyl} porphyrin (LD 4 ), with good water solubility, low toxicity and targeting characteristics, showed unique promotion of wound healing and immune regulation, as well inhibition of microbial pathogens in treatment of traumatic infection ( Xu et al, 2016 ; Zhao et al, 2021 ). On the basis of these results, we sought to determine whether this photosensitizer could regulate the microflora and treat UC.…”

Applications of Antimicrobial Photodynamic Therapy against Bacterial Biofilms

“…More importantly, it has enabled combination therapies involving PDT that successfully augment its bacterial and biofilm destruction mechanisms in many ways. Nanoconjugate-mediated combination with several known antibiotics such as vancomycin, minocycline, and cefepime have demonstrated the power of incorporating these drugs with the photodynamic photosensitizer in one nanoconjugate [ 107 , 108 , 109 , 110 , 111 , 112 ] while plasmonic nanoparticle-mediated combination with PTT [ 113 , 114 , 115 , 116 , 119 , 120 , 121 , 122 , 123 ] showed synergistic improvements in bacterial and biofilm eradication. Given that different antibiotic drugs have different mechanism and targets, the data presented by Pérez-Laguna et al (2021) on the use of more than one antibiotic drug in combination with PDT suggests that more research is needed to evaluate synergism and additivity [ 21 ].…”

“…In addition to the many case studies reported on the application of this combination therapeutic technology in periodontal therapy [ 87 , 88 ], enhancement of healing effects has also been demonstrated with the healing of third degree burn wounds infected with methicillin-resistant Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa in mice, using protoporphyrin IX as the aPDT photosensitizer and ceftriaxone as the antibiotic drug [ 110 ]. Furthermore, a clinical comparative study demonstrated improvement in clinical and histological outcomes of aPDT using indocyanine green as the photosensitizer, combined with antibiotic therapy using amoxicillin as the antibiotic drug, for pericoronitis treatment when compared with antibiotic therapy alone [ 111 ].…”