Photodynamic Therapy Using Systemic Administration of 5-Aminolevulinic Acid and a 410-nm Wavelength Light-Emitting Diode for Methicillin-Resistant Staphylococcus aureus-Infected Ulcers in Mice

Abstract

Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

“…The animal species used in the 19 studies were mice (n = 16) and rats (n = 3) . Of the 16 mouse studies, nine used BALB/c mice, 4 utilised Swiss albino mice, two used C57BL/ksj db/db mice, and one used CD1 mice . One study did not report the mouse strain that was used.…”

“…To investigate the antimicrobial effect of PDT, the wounds in all studies were inoculated with one or two species of bacteria. The majority were P. aeruginosa and methicillin‐resistant S. aureus . Others were unresistant S. aureus strains, Escherichia coli , and Acinetobacter baumannii …”

“…The second‐generation photosensitiser that is most commonly used in recent times is 5‐aminolevulinic acid. It was used in two studies . Other used photosensitisers were 5‐phenyl‐10; 15, 20‐tris (N‐methyl‐4‐pyridyl) porphyrin chloride (PTMPP); sinoporphyrin sodium (also known as DVDMS); indocyanine green (ICG); pentalysine β‐carbonylphthalocyanine zinc (ZnPc‐[Lys] 5 ); zinc phthalocyanine tetrasulfonate (ZnPc‐S 4 ); poly‐L‐lysine conjugate of chlorine p6 (pl‐cp6), β‐lactamase‐activated EtNBS (LAEtNBS); RLP068/Cl, toluidine blue O (TBO); polyethylenimine‐chlorin(e6) (PEI‐ce6); and poly‐ l ‐lysine‐chlorin e6 (pL‐ce6) …”

Cytotoxic Effects of Different ICG Concentrations and Laser Parameters on Neuroblastoma

“…PDT requires a chemical agent that is called as photosensitizer and activation of the agent by light of a specific wavelength to produce oxygendependent cytotoxic reaction [1][2][3] Indocyanine green (ICG), a photosensitizer with a molecular weight of 775 Da, has been used as a diagnostic agent to determine cardiac output, hepatic function and blood flow [4,5]. ICG has low toxicity and has been approved by Food and Drug Administration (FDA) [6].…”

Antibacterial photosensitization through activation of coproporphyrinogen oxidase

“…reaction, CPIII, a photoreactive molecule of demonstrated utility in treating bacterial infections (6,16,17). Photodynamic therapy (PDT) uses a photosensitizing molecule activated by a specific wavelength of light to produce reactive oxygen species that lead to cell death (6).…”