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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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