title: Ex vivo porcine vaginal mucosal model of infection for determining effectiveness and toxicity of antiseptics.
abstract: OBJECTIVE
  To develop a semi-high-throughput ex vivo mucosal model for determining efficacy and toxicity of antiseptics.
  
  
  RESULTS
  Explants (5 mm) from freshly excised, porcine vaginal mucosa were infected with methicillin-sensitive Staphylococcus aureus (1 × 10(6)  CFU) at the epithelial surface for 2 h. Haematoxylin and eosin staining revealed healthy uninfected tissue and only minor disruptions in tissue infected with methicillin susceptible Staph. aureus (MSSA), which remained in outer epithelial cell layers. After 2 h infection, 10 μl of chlorhexidine digluconate (CHG, 3%), povidone-iodine (PI, 7·5%), octenidine dihydrochloride (OCT, 0·1%) or polyhexamethylene biguanide (PHMB, 0·1%) was applied. Antiseptics significantly reduced MSSA (1-4 log10  CFU/explants) after 0·25 h to 4 h. CHG, PHMB and OCT exhibited persistence at 24 h. In broth culture, CHG 0·012% and PI 0·625% achieved >6 log10 reductions at 2 h. PI-based formulations were more efficacious than unformulated PI. PI-based formulations exhibited no significant cytotoxicity on explants using an MTT assay.
  
  
  CONCLUSIONS
  All antiseptics tested in the mucosal MSSA infection model reduced MSSA. CHG and PI were more potent in broth culture.
  
  
  CONCLUSIONS
  We developed a semi-high-throughput mucosal model that can identify compounds or formulations with promising antimicrobial and limited cytotoxic properties.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Anderson
authors.forename: M T
authors.initials: MT
authors.lastname: Scholz
authors.forename: P J
authors.initials: PJ
authors.lastname: Parks
authors.forename: M L
authors.initials: ML
authors.lastname: Peterson
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology* / Q000633:toxicity; D001645:Biguanides / Q000494:pharmacology / Q000633:toxicity; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009092:Mucous Membrane / Q000033:anatomy & histology / Q000382:microbiology*; D011206:Povidone-Iodine / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013552:Swine; D046509:Tissue Culture Techniques; D014621:Vagina / Q000033:anatomy & histology / Q000382:microbiology
chemical_list: D000891:Anti-Infective Agents, Local; D001645:Biguanides; C031233:polihexanide; D011206:Povidone-Iodine; C010882:chlorhexidine gluconate; D002710:Chlorhexidine
keywords: MRSA; antiseptic; decolonization; mucosal model; toxicity