title: Slow release iodine preparation and wound healing: in vitro effects consistent with lack of in vivo toxicity in human chronic wounds.
abstract: BACKGROUND
  Antiseptic agents, particularly slow-release preparations, are increasingly being used in the management of chronic wounds. One such agent, cadexomer iodine, carries iodine (0.9% weight/weight) immobilized in beads of dextrin and epichlorhydrin and has been demonstrated to be highly effective in promoting healing of exudative wounds. However, there have been no studies directly assessing the potential lack of toxicity of cadexomer iodine on human cutaneous tissues.
  
  
  OBJECTIVE
  To determine if, within a certain concentration range, cadexomer iodine is non-toxic to human cells and cutaneous tissue and to assess histologically human chronic exudative wounds that are being treated with cadexomer iodine.
  
  
  METHODS
  We examined the effects of varying concentrations of cadexomer iodine on the viability of human fibroblasts in culture (by trypan blue exclusion). The morphology, cellular proliferation capacity (measured by [3H]thymidine uptake), ability to produce alpha 1(I) procollagen chain mRNA, and cell outgrowth from neonatal foreskin explants were also evaluated in human fibroblasts after incubation with various concentrations of cadexomer iodine. Moreover, biopsies of chronic exudative wounds concurrently treated with cadexomer iodine were stained with haematoxylin and eosin or a Gram stain and evaluated microscopically.
  
  
  RESULTS
  At concentrations of up to 0.45%, cadexomer iodine was found to be non-toxic to fibroblasts in vitro; there were no changes in viability, morphology, cellular proliferation, ability to produce collagen, and cell outgrowth from explants. In vivo, skin biopsies of chronic exudative wounds being treated with cadexomer iodine demonstrated no evidence of cell necrosis, displayed re-epithelialization, and revealed bacteria within the cadexomer beads.
  
  
  CONCLUSIONS
  These studies demonstrate that cadexomer iodine has definite non-toxic concentration ranges for fibroblasts in vitro, which are consistent with a lack of cellular toxicity in human chronic exudative wounds treated with cadexomer iodine. Cadexomer iodine may also have the additional property of trapping microorganisms.
authors.affiliation: Department of Biochemistry, Roger Williams Medical Center, 50 Maude Street, Providence, RI 02908, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Zhou
authors.forename: W K
authors.initials: WK
authors.lastname: Nahm
authors.forename: E
authors.initials: E
authors.lastname: Badiavas
authors.forename: T
authors.initials: T
authors.lastname: Yufit
authors.forename: V
authors.initials: V
authors.lastname: Falanga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D017613:Iodine Compounds / Q000008:administration & dosage*; D007466:Iodophors; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects* / Q000382:microbiology; D012883:Skin Ulcer / Q000188:drug therapy* / Q000382:microbiology; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000891:Anti-Infective Agents, Local; D003692:Delayed-Action Preparations; D017613:Iodine Compounds; D007466:Iodophors; D011347:Procollagen; D012333:RNA, Messenger; C038634:cadexomer iodine; D013936:Thymidine