title: Surface chemistry study of the interactions of benzalkonium chloride with films of meibum, corneal cells lipids, and whole tears.
abstract: OBJECTIVE
  To perform a surface chemistry study of the interactions between benzalkonium chloride (BAC), a common preservative used in ophthalmic formulations, and tear film (TF) constituents.
  
  
  METHODS
  The interactions between BAC and human tears, meibum, and rabbit corneal cell lipid extracts at the air-water interface were examined in vitro during controlled compression-expansion of the film area by a Langmuir surface balance, surface potential measurements, and pendant drop-axisymmetric drop shape analysis (PD-ADSA). Surface pressure-area isotherms and isocycles were used to assess the sample's lateral elasticity and capability of compressing and spreading during dynamic area changes. Lipid film morphology was monitored by Brewster angle microscopy. The viability of BAC-treated Statens Seruminstitut rabbit cornea (SIRC) cell cultures was also examined. The BAC concentration was kept within the clinical range of 0.001% to 0.02%.
  
  
  RESULTS
  In the Langmuir balance and PD-ADSA experiments, the interactions between BAC and lipids or tears resulted in (1) impaired lipid spread and formation of discontinuous nonuniform surface layers, (2) increased surface pressure-area hysteresis during compression and expansion, and (3) displacement of the lipids by BAC from the surface. A decrease (>50%) in SIRC cell viability was observed. The effects occurred within seconds after BAC exposure, and their magnitude increased with BAC concentration.
  
  
  CONCLUSIONS
  The surface chemistry approach used in this study provided molecular-scale insights into the detrimental effect of BAC on TF, which well explain the TF instability and corneal epithelial barrier dysfunction after exposure to BAC in the in vivo human eye.
authors.affiliation: Department of Biochemistry, Faculty of Biology, University of Sofia, Bulgaria. ggeorg@biofac.uni-sofia.bg
authors.forename: Georgi A
authors.initials: GA
authors.lastname: Georgiev
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoi
authors.forename: Krassimir
authors.initials: K
authors.lastname: Koev
authors.forename: Elena
authors.initials: E
authors.lastname: Kutsarova
authors.forename: Slavyana
authors.initials: S
authors.lastname: Ivanova
authors.forename: Alexander
authors.initials: A
authors.lastname: Kyumurkov
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.forename: Rumen
authors.initials: R
authors.lastname: Krastev
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Lalchev
mesh_terms: D000328:Adult; D000818:Animals; D001548:Benzalkonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012634:Bodily Secretions / Q000187:drug effects; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008537:Meibomian Glands / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D010539:Permeability / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013499:Surface Properties / Q000187:drug effects; D013500:Surface Tension / Q000187:drug effects; D013666:Tears / Q000737:chemistry / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001548:Benzalkonium Compounds; D008563:Membrane Lipids; D011310:Preservatives, Pharmaceutical