title: Topical photodynamic treatment with poly-L-lysine-chlorin p6 conjugate improves wound healing by reducing hyperinflammatory response in Pseudomonas aeruginosa-infected wounds of mice.
abstract: 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/cm(2) 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/cm(2) 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.
authors.affiliation: Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013, India.
authors.forename: Khageswar
authors.initials: K
authors.lastname: Sahu
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Sharma
authors.forename: Harsha
authors.initials: H
authors.lastname: Bansal
authors.forename: Alok
authors.initials: A
authors.lastname: Dube
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Gupta
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity / Q000528:radiation effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects; D014946:Wound Infection / Q000188:drug therapy* / Q000473:pathology
chemical_list: D015850:Interleukin-6; D017319:Photosensitizing Agents; D014409:Tumor Necrosis Factor-alpha; C513585:polylysine-chlorin(E6) conjugate; D011107:Polylysine; D003094:Collagen