Abstract
PurposeTo assess the physicochemical properties of hyaluronic acid (HA)-based artificial tears.MethodsThe average molecular weight (MW) and polydispersion index (PDI) of HA in 18 commercially available artificial tears were determined by light scattering/high-performance liquid chromatography. Osmolality, pH, viscosity, and sodium concentration were determined using an osmometer, pH meter, rheometer, and inductively coupled plasma mass spectrometer, respectively.ResultsThe MW of HA varied considerably between formulations. The PDI was >2.0 in two formulations (2.28 and 4.94), suggesting the presence of a copolymer and/or HA size variability. Three formulations exhibited viscosity exceeding the blur threshold at different shear rates. Viscosity at low shear rates was generally highest in formulations containing high-MW HA. Correlations were found between observed viscosity and a predictive/calculated value, except for four copolymer-containing formulations, and osmolality (range, 154–335 mOsm/kg) and sodium concentration (range, 22–183 mM), with two exceptions. Compared with organic osmolytes, adding sodium decreased viscosity, particularly at lower shear rates.ConclusionsIn the context of the literature, our findings suggest that for most patients with dry eye disease, the ideal HA-based artificial tear should include high-MW HA with a low PDI and exhibit enhanced viscosity at low shear rate (without exceeding the blur threshold). The inclusion of synergistic copolymers and a low sodium concentration may increase viscosity, but whether any of these physicochemical properties or correlations can predict clinical efficacy will require further investigation.Translational RelevanceUnderstanding the properties of HA-based artificial tears will support the development of unique formulations that target specific ocular surface conditions.
Highlights
Artificial tears are designed to supplement or substitute for normal tears and alleviate dry eye disease
hyaluronic acid (HA) is a strongly hydrophilic, naturally occurring, nonsulfated glycosaminoglycan composed of disaccharide units of glucuronic acid and N-acetyl-D-glucosamine; its molecular weight (MW) ranges from,100 to
The two Optive products contain highMW HA (1178 kDa), the average MW of their polymer component was 318 kDa before the hyaluronidase treatment, decreasing to 201 kDa afterwards, which is consistent with low-MW CMC being a major contributor to the overall MW of those formulations, as previously reported.[35]
Summary
Artificial tears are designed to supplement or substitute for normal tears and alleviate dry eye disease. Available formulations contain hydrophilic polymers such as hyaluronic acid (HA) and/or cellulose ethers that augment viscosity, improve retention time, and optimize ocular surface hydration and lubrication.[1,2] HA is a strongly hydrophilic, naturally occurring, nonsulfated glycosaminoglycan composed of disaccharide units of glucuronic acid and N-acetyl-D-glucosamine; its molecular weight (MW) ranges from ,100 to .1000. HA provides viscoelasticity to biological fluids, such as the vitreous humor,[3,4] and induces cellular signaling in a size-dependent manner[5,6] by binding to CD44, a polymorphic glycoprotein receptor that is expressed ubiquitously[7,8] and has been implicated in the hydration of the ocular surface, as well as regeneration of the corneal epithelium.[9,10] Notably, TVST j 2019 j Vol 8 j No 6 j Article 2. CD44 is overexpressed in corneal/conjunctival cells where there is ocular surface damage.[11]
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