The evolution of artificial tears based on hyaluronic acid

In recent years, there has been growing interest in the use of tear substitutes, based on natural polysaccharides in the treatment of dry eye syndrome, the leader of which is hyaluronic acid (HA). It has sufficient biocompatibility, non-immunogenicity, high viscoelasticity, hydrophilic, mucus-adhesive and good moisturizing properties. At the same time, in order to improve artificial tear preparations, there is a need to improve the mechanical and rheological properties of HA, its hygroscopicity, swelling in an aqueous environment and reducing the rate of biodegradation. One of the ways to solve this problem was the chemical modification of HA, by cross-linking its chains with two or more covalent bonds, with the participation of various polyfunctional molecules: urea, HA-cysteine ethyl ester, polyfunctional diepoxides, glutaraldehyde, carbodiimide, and many others. At the same time, the rigidity of the three-dimensional polymer network increases, increasing its resistance to enzymatic decomposition at the site of burial. Cross-linked HA has a higher viscosity compared to native hyaluronic acid due to the binding of its chains, which determines longer retention on the corneal epithelium and naturally makes it possible to reduce the frequency of drug instillations. Convincing data were obtained on the effectiveness of the resulting cross-linked hydrogel with non-Newtonian properties in vitro – on cultures of corneal epithelial cells and in vivo – on models of mechanical trauma and chemical burns of the cornea, as well as in animals with torpid corneal ulcers. The clinical effectiveness of cross-linked hyaluronic acid in the treatment of patients with dry eye syndrome of varying severity, including those due to Sjögren’s syndrome, has also been established. The higher effectiveness of cross-linked HA compared to native HA preparations has been convincingly proven. Taking into account the available information, an official drug has been developed based on cross-linked 0.2% hyaluronic acid Ocutears® Hydro+ (Santen).