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Georgi Georgiev, Norihiko Yokoi, Slavyana Ivanova, Rumen Krastev, Zdravko Lalchev; Surface Chemistry Study Of The Interactions Of Benzalkonium Chloride and Hyaluronic Acid With Meibomian And Corneal Lipids. Invest. Ophthalmol. Vis. Sci. 2013;54(15):944.
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© ARVO (1962-2015); The Authors (2016-present)
Dodecyl dimethyl benzyl ammonium chloride (BAK) is commonly used preservative in eyedrop formulations, known to impair the integrity of the tear film lipid layer and of the corneal epithelium membranes. We studied the capability of high molecular weight (Mw 1x10+6) hyaluronic acid (HA; Santen Pharmaceutical, Osaka, Japan) to protect meibomian and corneal lipid films at the air/water interface from the adverse action of BAK.
Human meibum was collected from healthy volunteers; corneal lipids were extracted from SIRC cell culture. The interactions of BAK with meibomian and corneal lipids at the air/water interface in presence and absence of HA in the film subphase were examined in vitro at blink-like compression/expansion of film area by Langmuir surface balance. The sample’s lateral elasticity and capability to compress and spread during dynamic area changes were evaluated through the surface pressure-area isotherms and isocycles. The lipid films morphology was monitored by Brewster Angle Microscopy. BAK concentration was kept within the clinical range of 0.005-0.02%; HA was used in the range of 0.01-0.3%. The viability of SIRC cell cultures treated with BAK, pure and mixed with HA, was examined.
Pure BAK instantaneously inserted in the lipid films (corneal or meibomian). The interaction resulted in impaired spreading and discontinuous patchy structure of the lipid films, increased surface pressure-area hysteresis and partial displacement of the lipids by BAK from the surface. The inclusion of HA in the films subphase opposed to these adverse effects and at ≥ 0.1% HA the properties of the lipid films were maintained for the entire BAK concentration range. Identical results were obtained with cell culture experiments which showed that SIRC cells maintained high viability at ≥ 0.1% HA.
HA at concentration ≥ 0.1% HA was able to efficiently suppress the adverse effects of BAK on the properties of meibomian and corneal lipid films and on the viability of SIRC cells. Thus mixtures of BAK and HA represent prospective compositions for eyedrop formulations. Surface chemistry based approach is proposed for in vitro molecular scale characterization of pharmaceutically applicable polymers and their interactions with tear film lipids.
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