Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View.

Lukasz Cwiklik,Agnieszka Olżyńska,Philippe Daull,Georgi As Georgiev,Petar Eftimov,Jean-Sebastien Garrigue,Adéla Melcrová

doi:10.3390/ijms21249490

Abstract

The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops–tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear–air interface.

Highlights

The ocular surface is covered by a thin film of tears structured in three layers: a mucin layer, the aqueous phase of the tear film (TF), and the TF lipid layer (TFLL) [1,2]
We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids
We investigate two components targeted to the TFLL/aqueous tear interface: (i) cetalkonium chloride (CKC), a long chain (C-16) cationic lipid thought to match with acyl chains of meibomian lipids, and (ii) poloxamer 188 (P188), which is often used as a pharmaceutical ingredient

Summary

Introduction

The ocular surface is covered by a thin film of tears structured in three layers: a mucin layer, the aqueous phase of the tear film (TF), and the TF lipid layer (TFLL) [1,2]. Oil-in-water emulsions supplying nonpolar lipids [10] and surface-active agents at the air/tear surface were demonstrated to improve the clinical signs and symptoms of DED [11,12] and MGD patients [13] with significant improvements of TFBUTs. A specific role of surfactant species in such oil-in-water emulsions was found to be responsible for their favorable interactions with meibomian gland secretion (MGS) [14]. We investigate two components targeted to the TFLL/aqueous tear interface: (i) cetalkonium chloride (CKC), a long chain (C-16) cationic lipid thought to match with acyl chains of meibomian lipids, and (ii) poloxamer 188 (P188), which is often used as a pharmaceutical ingredient Both molecules are surface-active and may act in a polar lipid-like fashion and can potentially alter the TFLL properties and TF stability [10]. We use a multi-scale approach employing various models of TFLL, ranging from Langmuir surface balance experiments on human MGS through to measurements using synthetic lipid films, down to molecular-level simulations employing in silico models of TFLL

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Conclusion