title: In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops.
abstract: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops.
  
  
  
  We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1®), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made.
  
  
  
  Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops.
  
  
  
  In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene®for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments.
authors.affiliation: 1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .|2 Department of Pharmacy, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS) , Santiago de Compostela, Spain .|3 Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII) , Santiago de Compostela, Spain .
authors.forename: Anxo
authors.initials: A
authors.lastname: Fernández-Ferreiro
authors.affiliation: 4 Department of Ophthalmology, Hospital de Conxo , Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain .
authors.forename: María
authors.initials: M
authors.lastname: Santiago-Varela
authors.affiliation: 4 Department of Ophthalmology, Hospital de Conxo , Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain .|5 Instituto Oftalmológico Gómez-Ulla , Santiago de Compostela, Spain .
authors.forename: María
authors.initials: M
authors.lastname: Gil-Martínez
authors.affiliation: 2 Department of Pharmacy, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS) , Santiago de Compostela, Spain .|3 Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII) , Santiago de Compostela, Spain .
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Barcia
authors.affiliation: 1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
authors.forename: Andrea
authors.initials: A
authors.lastname: Luaces-Rodríguez
authors.affiliation: 1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
authors.forename: Victoria
authors.initials: V
authors.lastname: Díaz-Tome
authors.affiliation: 6 Obesidomic Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII) , Santiago de Compostela, Spain .
authors.forename: María
authors.initials: M
authors.lastname: Pardo
authors.affiliation: 1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
authors.forename: José Blanco
authors.initials: JB
authors.lastname: Méndez
authors.affiliation: 4 Department of Ophthalmology, Hospital de Conxo , Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Piñeiro-Ces
authors.affiliation: 4 Department of Ophthalmology, Hospital de Conxo , Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain .
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Rodríguez-Ares
authors.affiliation: 2 Department of Pharmacy, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS) , Santiago de Compostela, Spain .|3 Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII) , Santiago de Compostela, Spain .
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Lamas
authors.affiliation: 1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Otero-Espinar
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000633:toxicity*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002710:Chlorhexidine / Q000008:administration & dosage / Q000633:toxicity*; D003315:Cornea / Q000187:drug effects; D060527:Corneal Keratocytes / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects; D006801:Humans; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D001550:Benzamidines; D009883:Ophthalmic Solutions; C046651:propamidine isethionate; D002710:Chlorhexidine
keywords: Acanthamoeba; chlorhexidine; cornea; eye drops; keratitis; propamidine; toxicology