Hyaluronic acid (sodium hyaluronate) and xanthan gum: valuable allies for the well-being of the ocular surface

New formulations for artificial tears more effective against dryness and ocular discomfort

Sodium hyaluronate and xanthan gum in artificial tears

Currently available artificial tear formulations contain hydrophilic polymers such as sodium hyaluronate (hyaluronic acid, HA) and/or cellulose ethers that increase viscosity, improve retention time and optimise hydration and lubrication of the ocular surface.

The sodium hyaluronate is an anionic glycosaminoglycan with a viscoelastic rheology. Although mainly found in connective tissue, it is also highly concentrated in the vitreous humour and aqueous humour, where it coats the corneal endothelium. HA is widely used in lubricants used to treat DES because it effectively binds water, resists dehydration and shows excellent biocompatibility. Many studies have revealed that HA protects corneal epithelial cells from damage, stimulates epithelial migration and improves the optical quality of the retinal image. Artificial HA lacrimals have also been shown to help repair ocular surface irregularities, stabilise the pre-corneal tear film and mitigate the intensity of dry eye symptoms.

Another natural polymer used in the most current artificial tear formulations is the xanthan gum (xanthan gum, XG), a complex exopolysaccharide used as a food additive and rheological modifier (rheology is the science that studies the equilibria achieved in matter deformed by stress). Its chemical structure, rich in OH groups, shows the ability to react with reactive oxygen species (ROS) indicating its role as an antioxidant molecule.

Lo oxidative stress is caused by an imbalance between the production of reactive oxygen species and the ability of the defence mechanisms of biological systems to eliminate stress. It is now widely recognised that oxidative stress is involved in many acute and chronic diseases, and in the normal ageing process, and also thedry eye has been recognised as a oxidative stress-induced syndrome. Whatever the initial mechanism, dry eye causes an epithelial lesion that induces local inflammatory reactions; it is hypothesised that subclinical hormonal or autoimmune factors, aggravated by exogenous factors (pollution, local infection, ultraviolet irradiation, tobacco smoke or allergic or iatrogenic phenomena), lead to a cascade of cellular reactions to which apoptosis (programmed cell death) may be closely related.

Xanthan gum has rheological properties similar to hyaluronic acid and normal tears; but compared to HA, which degrades rapidly in vivo, it is much more stable over a wide range of pH, ionic strength and temperature.

XG and HA also show a synergistic effect on the corneal abrasions which are characterised by acute ocular pain and other symptoms of discomfort affecting the quality of life of patients. In corneal abrasion, hydration and lubrication prevent friction by decreasing surface disorder and promoting recovery of the corneal epithelial defect. Hyaluronic acid and xanthan gum are high molecular weight polysaccharides and help protect the cornea by retaining fluid and ensuring hydration.

Currently, an innovative hypotonic formulation containing a combination of hyaluronic acid sodium salt, xanthan gum and osmoprotectants such as betaine and glycine is being launched. This formulation, in addition to moisturising and lubricating, is designed to compensate for tear instability, restore tear volume, provide antioxidant and osmoprotective properties, and thus rebalance the wellbeing of the ocular surface.

Eye surface disorders and tear film

The ocular surface includes the cornea, conjunctiva, eyelids and tear glands, so any disorder affecting these structures can be classified as Ocular Surface Disease (OSD).

Among ocular surface disorders the dry eye syndrome (DES - Dry Eye Syndrome) is a very common condition that has a major impact on the patient's daily activities, such as using computers and smartphones or reading.

In addition to DES, the incidence of eye drynessa very common cause of discomfort, is on the rise due to the increasing use of digital tools and in this pandemic period, the prolonged use of the surgical mask, a prescription widely used to counteract the spread of Sars-CoV-2, is often associated with dry eye.

Artificial tears are the most traditionally used therapeutic aid for DES and to counteract dry eye discomfort and should not be confused with eye drops. They usually consist of a physiological saline solution with a variety of surface lubricants, which improve viscosity and are formulated to replace and/or supplement the natural tear film.

The tear film, the film that covers the corneo-conjunctival surface, is composed of three layers: an outer lipid layer produced by the Meibomian glands, a central aqueous layer produced by the main and accessory lacrimal glands, and an inner mucin layer produced by the calyciform cells of the conjunctiva. Recently, the hypothesis has been put forward that the aqueous and mucin layers are a single layer of mucous/aqueous gel.

 

Bibliography

In Cheon You et al. Comparison of 0.1%, 0.18%, and 0.3% Hyaluronic Acid Eye Drops in the Treatment of Experimental Dry Eye. Journal of Ocular Pharmacology and Therapeutics. Volume 34, Number 8, 2018

Carla Amico et al. Antioxidant Effect of 0.2% Xanthan Gum in Ocular Surface Corneal Epithelial Cells. Current Eye Research, Early Online, 1-5, 2014.

Tolga Kocatürk et al. Combined eye gel containing sodium hyaluronate and xanthan gum for the treatment of the corneal epithelial defect after pterygium surgery. Clinical Ophthalmology 2015:9 1463-1466.

Majid Moshirfar et al. Face Mask-Associated Ocular Irritation and Dryness, Ophthalmol Ther (2020) 9:397-400.

Dr. Carmelo Chines
Direttore responsabile

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