Hydroxypropyl-guar (HPG) is a thickening agent first added to lubricating eye drops in 2003. This agent, which enhances viscosity, has been used in the SYSTANE® family of lubricant eye drops (Alcon Laboratories, Inc., Fort Worth, TX, USA). HPG forms a partially linked gel with borate to prolong the retention of demulcents, such as polyethylene glycol and propylene glycol, on the eye. This helps to protect the ocular surface, thereby reducing the symptoms of dry eye disease (DED). The definition of DED has evolved with advances in research, leading to changes in HPG-containing eye care solutions. This article reviews current knowledge on the use of HPG-containing lubricating eye drops in the management of DED.

Artificial lipid-containing tear formulations are developed to reduce tear evaporation by the restoration of a deficient tear lipid layer. Artificial tear formulations that prevent cell desiccation will result in ocular surface protection and the maintenance of cell metabolic activity. During dehydration, cells undergo the process of loss of metabolic activity and subsequently cell death. This work describes a method for assessing the efficacy of artificial tear formulations. The metabolic dye (i.e., alamarBlue) changes from a low fluorescent molecule resazurin to a fluorescent molecule resorufin in viable cells. The biological performance of an artificial tear formulation is measured as the ability of the formulation to (a) maintain cell viability and (b) provide cell protection from desiccation. Growth media and saline are used as controls for the cell viability/desiccation tests. Cells are incubated with test solutions for 30 min and then desiccated for 0 or 5 min at 37 °C and 45% relative humidity. Cell metabolic activity after initial exposure and after cell desiccation is then determined. The results show the comparative effects of eye drop formulations on cell metabolic activity and desiccation protection. This method can be used to test dry eye formulations that are designed to treat individuals with evaporative dry eye.

PURPOSE:To evaluate the effect of hydroxypropyl-guar anionic phospholipid nanoemulsion (HP-guar nanoemulsion), a new artificial tear formulation for treatment of dry eye disease (DED), in corneal epithelium models.METHODS:Cultured human corneal epithelial cells were used to assess (1) hydration protection and hydration retention protection against desiccation, and (2) cell recovery after benzalkonium chloride (BAC) damage. Corneal epithelium permeability was measured by 5,6-carboxyfluorescein (CF) uptake in intact rabbit eyes. Lubricity was determined using simulated blinking in bovine pericardium-pericardium tribological experiments; elastic filament strength was measured using an extensional rheometer. Comparator arms included vehicle/control and the microemulsion [Systane® Balance (SYSB)].RESULTS:Cell hydration protection was 39.5%, 7.1%, and -0.1%, and surface hydration retention was 32.6%, 11.0%, and -1.2% with HP-guar nanoemulsion, SYSB, and vehicle, respectively, after desiccation. After 48 h, cell recovery from BAC exposure (relative fluorescence units ± SD) was faster with HP-guar nanoemulsion treatment (2.66 ± 0.2) than SYSB (2.76 ± 0.2) and vehicle (3.11 ± 0.4). The CF permeability (ng CF/g) decreased in rabbit cornea treated with HP-guar nanoemulsion (9.6 ± 2.3) than those with SYSB (13.12 ± 2.8) or BAC-exposed cornea (22.6 ± 5.1). HP-guar nanoemulsion demonstrated greater lubricity and polymer filament break-up time than SYSB and vehicle. In all assessments, HP-guar nanoemulsion showed significant improvement versus vehicle/control (P < 0.05); outcomes were better with HP-guar nanoemulsion versus microemulsion.CONCLUSIONS:The HP-guar nanoemulsion promotes greater moisture retention, protection, improved cell barrier function, and increased elastic filament strength in corneal epithelium models. The potential clinical benefits of HP-guar nanoemulsion needs to be evaluated in patients with DED, in future studies.

Abstract Purpose: Hydroxypropyl guar (HPG) and hyaluronic acid (HA) have been individually shown to improve dry eye symptoms. The purpose of this in vitro study was to assess the potential benefits of a new lubricant eye drop formulation containing the demulcents propylene glycol and polyethylene glycol and an HA/HPG dual polymer in models of the human corneal epithelium. Methods: Cultured human corneal epithelial or corneal-limbal epithelial cells were treated with the HA/HPG dual-polymer formulation or single-polymer formulations containing either HPG or HA. Desiccation protection by cell hydration and surface retention was assessed using cell viability assays. Sodium fluorescein permeability, transepithelial resistance, and cell viability assays were conducted using pretreated cells exposed to a surfactant/detergent insult to evaluate cell and cell barrier protection. Surface lubricity was assessed in tribological experiments of pericardium–pericardium friction. Results: Hydration protection against desiccation and protection by surface retention were significantly greater with the HA/HPG formulation versus HPG or HA (P<0.001) alone and with HPG versus HA (P≤0.016). Fluorescein permeability and transepithelial resistance assays demonstrated significantly better cell and barrier protection from surfactant insult with HA/HPG versus the single-polymer formulations (P≤0.01). After insult, there were markedly more viable cells evident with HA/HPG compared with HPG or HA alone. HA/HPG and HPG reduced surface friction to a greater extent than HA (P≤0.02) and maintained lubricity after the formulations were rinsed away. Conclusions: HA/HPG provided effective hydration and lubrication and demonstrated prolonged retention of effect. HA/HPG may potentially promote desiccation protection and retention on the ocular surface.

The formulation of dilute, transparent ophthalmic emulsions (eye drops) with long shelf lives is a challenge because of the tendency of the emulsion droplets to aggregate, particularly in the presence of the water-soluble polymers typically used in eye drops. While many functions of eye drops, such as lubricity and residence time in the eye, are promoted by high concentrations of high molecular weight water-soluble polymers, emulsified lipids and drugs aggregate in the eye drop bottle if the polymer concentration is above the critical flocculation concentration (CFC). The purpose is to develop a simple approach to predict the CFC for polymers based on information readily available in the literature. High molecular weight guar was hydrolyzed to give a series of guar samples spanning a wide range of average molecular weights. The CFC values and critical viscosity concentrations were measured as functions guar properties, using electrophoresis, dynamic light scattering and rheology measurements. The higher the guar molecular weight, the lower was the CFC, the maximum concentration that can be tolerated in the eye drop formulation. The guar CFC values were approximately equal to the overlap concentrations where guar molecules start to overlap in solution. We propose that the CFC can be estimated for any water-soluble polymer using the polymer molecular weight and the readily available Mark Houwink parameters, thus providing a design rule for ophthalmic emulsions. (C) 2014 Elsevier B.V. All rights reserved.

This initial study shows that hydrophobic modification of guar polymers used in eye drops forms weak gels with human serum albumin (HSA), suggesting that modified guar may offer advantages for treatment of dry eye diseases that lead to elevated HSA concentrations in tears. Specifically, hydroxypropyl guar samples were oxidized and derivatized with linear alkyl amines to give a series of modified guar polymers (MGuar) bearing hydroxypropyl, N-alkylamide, and carboxyl moieties. MGuar interactions with lysozyme and HSA were measured by binding and rheological methods as functions of the alkyl chain length and the extent of hydrophobic modification. HSA binds MGuar, giving weak gels, whereas lysozyme shows little tendency to bind MGuar or to interfere with HSA binding. Six mole percent substitution of decyl hydrophobes gave the strongest gels in the presence of HSA.

Purpose.: To study melting characteristics and the morphology of human and mouse meibum. Methods.: Hot stage cross-polarized light microscopy (HSPM) and immunohistochemical approaches were used. Results.: Isolated human meibum, and meibum of mice (either isolated or within the meibomian ducts of mice), were found to be in liquid-crystal state at physiological temperatures. Melting of both types of meibum started at approximately 10°C and was completed at approximately 40°C. Melting curves of isolated meibum and meibum inside the meibomian ducts were multiphasic with at least two or three clearly defined phase transition temperatures, typically at approximately 12 ± 2°C (minor transition), 21 ± 3°C, and 32 ± 3°C, regardless the source of meibum. Melting was highly cooperative in nature. Samples of abnormal human meibum collected from dry eye patients with meibomian gland dysfunction often showed an increased presence of nonlipid, nonmelting, nonbirefringent, chloroform-insoluble inclusions of a protein nature. The inclusions were positively stained for cytokeratins. The presence of these inclusions was semiquantitatively characterized using a newly proposed 0 to 4 scale. In the presence of large amounts of these inclusions, melting characteristics of meibum and its structural integrity were altered. Conclusions.: HSPM is an effective tool that is suitable for biophysical and morphological evaluation of meibum. Morphological properties and melting characteristics of human meibum were found to be similar to those of mice. Abnormal meibum of many dry eye patients contained large quantities of nonlipid, protein-like inclusions, which were routinely absent in meibum of normal controls.

PURPOSE/AIM:The meibomian lipid layer is able to withstand the enormous stresses and deformations that occur during blinking due to the combination of its elastic and viscous properties. The purpose of this study was to measure the dilatational viscoelasticity of in vitro meibomian lipid films and compare how these properties differ between room temperature and physiological temperatures. Viscoelasticity was also compared with meibomian lipid films seeded with cholesterol or β-carotene (the levels of these lipid species change in disease states). MATERIALS AND METHODS:Dilatational viscoelasticity (E) was measured using an oscillating pendant drop method. Measurements were carried out on spread films at the air-water interface as a function of frequency (0.1256-12.56 rad/s) at various temperatures between 18-43 °C. RESULTS:Generally, E gradually decreased as the overall temperature was increased. At both 37 and 20 °C, films demonstrated that the elastic modulus (E') was more dominant than the viscous modulus (E″), indicating films were more solid-like than fluid-like, regardless of temperature. E' and E″ were also dependant on frequency, indicating some molecular rearrangements of the lipid molecules as films were compressed and expanded. Films seeded with cholesterol or β-carotene showed a modest increase in the moduli. CONCLUSIONS:These results are consistent with previous findings which have predicted and indicated that the meibomian lipid layer is a viscoelastic film at the air-liquid interface. These properties are integral to how the tear film lipid layer is able to maintain its structure, and hence integrity of the ocular surface.

La presente invention concerne des compositions de gouttes artificielles et des compositions ophtalmiques appropriees pour la delivrance de medicament. Dans une forme de realisation de la presente invention, les compositions comprennent un polymere de galactomannane comme le guar ou l'hydroxypropyle guar, de l'acide hyaluronique et un cis-diol comme le sorbitol. Dans une forme de realisation preferee, les compositions comprennent aussi un compose de borate.