Surface chemistry study of the interactions of hyaluronic acid and benzalkonium chloride with meibomian and corneal cell lipids

Abstract

Hyaluronic acid (HA) is a non-surface active water soluble anionic polyelectrolyte found in sub-nanomolar levels in human tears and implemented in substitutes of human tears' aqueous layer. In the current work we studied the interactions of high molecular weight (M w 1 Â 10 6 Da) HA with films of ocular surface lipids and investigated the potential of HA to modify the interactions of the lipid films with the low M w cationic surfactant dodecyldimethylbenzylammonium chloride (C12-BAC) known for its adverse effects on tear film compounds. The interactions of HA and/or C12-BAC with meibomian and corneal lipid films were examined using a Langmuir surface balance. The film morphology was monitored by Brewster Angle Microscopy. The HA/C12-BAC interactions at the air/water interface and in the solution bulk were also examined. HA interacted with meibomian lipids and enhanced the structure and the rheological properties of the meibum films. HA bound C12-BAC in bulky polymer/surfactant complexes and at $0.1% HA neutralized the capability of C12-BAC to penetrate the lipid layers and to disrupt their integrity and viscoelasticity. The results were correlated with the capability of HA to maintain the viability of C12-BAC treated corneal cells. Our study suggests a possible novel implementation of high M w anionic polyelectrolytes like HA: the polymers can be instilled on the ocular surface together with cationic surfactant containing drugs, and increase the biocompatibility of the ophthalmic formulations.A molecular scale mechanism is proposed for the interactions of HA with tear lipids and cationic surfactants.

Surface properties and exponential stress relaxations of mammalian meibum films

“…An inflexion point can be seen for all π/Cs −1 curves at <5 mN/m. Similar shape and value range of the π/Cs −1 curves was observed (Georgiev et al 2011(Georgiev et al , 2012(Georgiev et al , 2013(Georgiev et al , 2014 for human meibum films (inset in Fig. 4) but in their case the inflexion point was positioned at higher π's (8-10 mN/m) at 25 °C.…”

“…The fitting of the curves to a sum of decaying exponents allows identification of the number of processes involved in the reorganization of the heterogeneous film constituents and their characteristic times and how these depend on the temperature (Georgiev et al 2011(Georgiev et al , 2012Tschoegl 1989;van Hunsel and Joos 1989). The results are discussed in the context of the data on the surface properties and viscoelasticity of human meibum reported previously (Georgiev et al 2010(Georgiev et al , 2011(Georgiev et al , 2012(Georgiev et al , 2013(Georgiev et al , 2014Ivanova et al 2015;Leiske et al 2010). …”

“…Experiments were performed at two temperatures: 25 and 35 °C. The consensus mean temperature of the central cornea in humans, as obtained by infrared thermography, is 34-35.11 °C (Abreau et al 2016) and 35 °C was implemented as aqueous subphase temperature in numerous studies of human meibum films Georgiev et al 2012Georgiev et al , 2013Georgiev et al , 2014Ivanova et al 2015;Leiske et al 2012;Mudgil and Millar 2011;Raju et al 2013;Shrestha et al 2011). It was shown (Biondi et al 2015;Maggs 2008;Rysa and Sarvaranta 1974;Schwartz and Feller 1962) that although the body temperature of small mammals like dogs and cats is higher than in humans, the corneal surface temperature of these animals varies greatly depending on the environmental conditions and the location of measurement over the cornea; in a room with still air, it does not exceed 35.6 °C, which is very close to that of humans.…”

“…In order to facilitate the comparison of the surface properties and structure of canine and feline meibum films with those of human meibum (hMGS) layers and the corresponding discussion, representative reference data are taken from our previous studies (Georgiev et al 2010(Georgiev et al , 2012(Georgiev et al , 2013(Georgiev et al , 2014Ivanova et al 2015). These data are presented as insets in Figs.…”

The Effect of Ambient Ozone on Unsaturated Tear Film Wax Esters

“…14,35 Due to this, an approach of using multiple compression-expansion cycles has been adopted in studies using Langmuir films. 30,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] However, this approach relies on the assumption that the lipid films remain chemically stable for the duration of the experiment, which is not the case for unsaturated WEs in ambient air. Also, measurements on unsaturated CEs have shown time-dependent changes in the isotherms due to autoxidation.…”