July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Influence of benzylalkonium chloride on Tear Film Lipid Layer stability: a molecular level view by employing in silico modeling
Author Affiliations & Notes
  • Lukasz Cwiklik
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Kamila Riedlova
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Adela Melcrova
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Agnieszka Olzynska
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Philippe Daull
    Novagali Innovation Center, Santen SAS, Evry, France
  • Jean-Sebastien Garrigue
    Novagali Innovation Center, Santen SAS, Evry, France
  • Footnotes
    Commercial Relationships   Lukasz Cwiklik, Santen SAS (F); Kamila Riedlova, None; Adela Melcrova, Santen SAS (F); Agnieszka Olzynska, None; Philippe Daull, Santen SAS (E); Jean-Sebastien Garrigue, Santen SAS (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3279. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Lukasz Cwiklik, Kamila Riedlova, Adela Melcrova, Agnieszka Olzynska, Philippe Daull, Jean-Sebastien Garrigue; Influence of benzylalkonium chloride on Tear Film Lipid Layer stability: a molecular level view by employing in silico modeling. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3279.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Benzylakonium chloride (BAK) is a mixture of aliphatic C12 and C14 quaternary ammoniums. They were traditionally used to preserve eye drops through their bactericidal and bacteriostatic properties. It can be assumed that on the ocular surface these compounds significantly influence the stability of the Tear Film Lipid Layer (TFLL). Indeed, BAK was demonstrated to decrease the breakup time in patients. The amphiphilic and highly water soluble C12 and C14 BAK molecules are expected to act predominantly at the aqueous-lipid interface. As we demonstrated in earlier studies, the details of molecular-level interactions between individual species of TFLL are governing macroscopic behavior of the film, in particular its organization and stability. We hypothesize that C12 and C14 BAK can deplete the TFLL-water interface from its polar lipids upon blinking, resulting in the destabilization of the tear film.

Methods : Molecular dynamics simulations employing in silico TFLL model in contact with aqueous subphase were performed. The model includes several types of polar and nonpolar lipids as well as BAK molecules of various aliphatic chain length employing the coarse grain MARTINI model. Microsecond-long simulations of laterally relaxed and compressed TFLL with varying lipid, BAK content were performed.

Results : Models of TFLL deficient in polar lipids exhibit poration of the polar lipid sublayer and enhanced unfavorable contacts between water and triglycerides. Moreover, wetting properties of such films are reduced. In such systems, C12 and C14 BAK surfactant molecules locate predominantly at the water-lipid interface and interact with the polar lipids. Notably, long-chain BAK molecules partially prevent unfavorable water-lipid interactions and enhance wetting. Exact localization and stability of different BAK species depends on their alkyl chain length.

Conclusions : In silico simulations of TFLL-mimicking models support the hypothesis that behavior of BAK molecules in the tear film lipid layer and their influence on the lipid film properties depend on their alkyl chain length. C12 and C14 BAK molecules destabilize the TFLL and its water interface, while long-chain BAK molecules are particularly effective in reversing unfavorable water-lipid interactions and enhancing the film wetting.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×