title: Influence of different additives and their concentrations on corneal toxicity and antimicrobial effect of benzalkonium chloride.
abstract: OBJECTIVE
  The aim of this study was to examine the ophthalmic additives responsible for modulating acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) and investigate the ability of polyoxyethylene hydrogenated castor oil 40 (HCO-40) and polysorbate 80 (PS-80) to reduce the corneal toxicity and antimicrobial effects of BAC.
  
  
  METHODS
  Cytotoxicity of the additives, which included glycerin, polyvinyl alcohol, propylene glycol, polyethylene glycol, and PS-80, on rabbit corneal epithelial cells was examined using the cell proliferation assay in the presence and absence of 0.02% BAC. The corneal transepithelial electrical resistance change after a 60-second exposure to HCO-40 or PS-80 mixed with 0.02% BAC was measured in living rabbits. Corneal damage was examined using scanning electron microscopy. The antimicrobial activities of HCO-40 and PS-80 with 0.02% BAC against Staphylococcus aureus, Propionibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae were assessed.
  
  
  RESULTS
  Of all the tested additives, only PS-80 could prevent the BAC-induced cytotoxicity. Corneal epithelial barrier function disorder caused by 0.02% BAC was significantly alleviated by either PS-80 or HCO-40 in a concentration-dependent manner. Scanning electron microscopy images showed an improvement of BAC-induced corneal epithelial toxicity after the addition of HCO-40 or PS-80. The antimicrobial effect of the BAC against P. aeruginosa, E. coli, and S. pneumoniae was reduced after adding HCO-40 or PS-80.
  
  
  CONCLUSIONS
  HCO-40 and PS-80 reduce acute corneal toxicity and the antimicrobial effect of BAC. Possible interactions between BAC and other additives should be taken into consideration when evaluating the toxicity and antibacterial properties of BAC.
authors.affiliation: *Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and †Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Onizuka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uematsu
authors.forename: Mao
authors.initials: M
authors.lastname: Kusano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D001548:Benzalkonium Compounds / Q000633:toxicity*; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000648:ultrastructure; D017097:Electric Impedance; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D005990:Glycerol / Q000633:toxicity; D008297:Male; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D009883:Ophthalmic Solutions / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000633:toxicity; D011136:Polysorbates / Q000494:pharmacology*; D011142:Polyvinyl Alcohol / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D019946:Propylene Glycol / Q000633:toxicity; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000502:physiology
chemical_list: D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011136:Polysorbates; D011310:Preservatives, Pharmaceutical; D011092:Polyethylene Glycols; C023040:polyethoxylated castor oil; D019946:Propylene Glycol; D002368:Castor Oil; D011142:Polyvinyl Alcohol; D005990:Glycerol