Effectiveness of a single treatment of photodynamic therapy using topical administration of 5-aminolevulinic acid on methicillin-resistant Staphylococcus aureus-infected wounds of diabetic mice.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most important representative pathogen which causes clinically relevant infections in diabetic ulceration. We report our investigations on the efficacy of antimicrobial photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) on diabetic murine infected wound models induced with a MRSA SA325 strain. A solution of 10 % 5-aminolevulinic acid (ALA) was placed into the wounds followed by delivery of 25 J/cm2 (635 nm). The ALA-PDT treated wounds healed earlier as compared to others (P < 0.5). A significant reduction of bacterial counts (2.05 logs) was detected in wounds after ALA-PDT on Day 2 (P < 0.5). Additionally, histological analysis revealed that wounds treated with ALA-PDT exhibited a more complete re-epithelialization, blood micro-vessels, collagen-volume fraction and considerable decrease in inflammatory cells infiltration. Immunohistochemistry assay demonstrated considerable reduction of proinflammatory cytokines interleukin-1β (IL-1β), earlier expression of vascular endothelial growth factor A (VEGF-A), increase of basic fibroblast growth factor (bFGF) and Ki-67 in the ALA-PDT group (P < 0.5). These data imply that the therapeutic effect of ALA-PDT revealed an accelerated diabetic wound closure rate, together with reduced hyperinflammatory response and elevated growth factors.