Topical photodynamic treatment with poly-l-lysine–chlorin p6 conjugate improves wound healing by reducing hyperinflammatory response in Pseudomonas aeruginosa-infected wounds of mice

We report the results of our investigations on the effect of antimicrobial photodynamic treatment (APDT) with poly-lysine-conjugated chlorin p6 (pl–cp6) on proinflammatory cytokine expression and wound healing in a murine excisional wound model infected with Pseudomonas aeruginosa. Treatment of infected wounds with pl–cp6 and light doses of 60 and 120 J/cm² reduced the bacterial load by ~1.5 and 2.0 log, respectively, after 24 h. The treated wounds healed ~5 days earlier as compared to untreated control and wound closure was not dependent on light dose. Interestingly, at 96 h post-treatment, drug-treated wounds irradiated at 60 J/cm² showed considerable reduction of proinflammatory cytokines IL-6 (approximately five times) and TNF-α (approximately four times) compared to untreated control. Further, exposure of culture supernatants to similar light dose and pl–cp6 concentration under in vitro conditions reduced the protease activity by ~50 % as compared to the untreated control, suggesting inactivation of extracellular virulent factors. Additionally, histological analysis of treated infected wounds showed complete reepithelialization, ordered collagen fibers, and considerable decrease in inflammatory cell infiltration compared to untreated wounds. These results imply that pl–cp6-mediated PDT reduces hyperinflammatory response of infected wounds, leading to acceleration of wound healing.