Abstract
Polymer-based eye drops are the most used drug delivery system to treat dry eye disease (DED). Therefore, the mucoadhesion between the polymer and the ocular mucin is crucial to ensure the efficacy of the treatment. In this context, the present study aimed to evaluate the potential use of in vitro methods to study the mucoadhesion of eye drop solutions and, specifically to evaluate the efficacy of two hyaluronic acid-based formulations (HA), HA 0.15% and 0.30% (w/v) to treat DED. Rheology methods and zeta potential determination were used to study the mucoadhesive properties of both eye drop solutions. All results indicated that interactions occurred between the mucin and the HA, being stronger with HA 0.30%, due to the physical entanglements and hydrogen bounding. In vitro tests on ARPE-19 cell line were performed using a 2D and a 3D dry eye model and the results have shown that pre-treated cells with HA showed a morphology more similar to the hydrated cells in both products, with a high survival rate. The in vitro techniques used in this study have been shown to be suitable to evaluate and predict mucoadhesive properties and the efficacy of the eye drops on relief or treatment of DED. The results obtained from these methods may help in inferring possible in vivo effects.
Highlights
Dry eye disease (DED), known as keratoconjunctivitis sicca, is a pathology whose origin comes from several factors, resulting in symptoms of discomfort, visual disturbance, tear film instability with potential damage to the ocular surface, increased osmolality of the tear and inflammation
The results have shown that the cells who were not treated with hyaluronic acid-based formulations (HA) presented a disintegrated and dry membrane with a cell mortality rate close do 50% when compared to the non-dehydrated cells
In the 3D model the results show that the application of all three formulations obtained over 100% cell viability, meaning that the application of these medical devices (MD) provided a more suitable environment for cell proliferation
Summary
Dry eye disease (DED), known as keratoconjunctivitis sicca, is a pathology whose origin comes from several factors, resulting in symptoms of discomfort, visual disturbance, tear film instability with potential damage to the ocular surface, increased osmolality of the tear and inflammation. Generalized inflammatory autoimmune diseases of the lacrimal gland are responsible for aqueous tear deficiency and excessive tear evaporation which causes the dry eye sensation [1,2,3]. Non-disease-related factors can cause an alteration to the evaporation rate, including ambient conditions, hormonal regulation, blink rate, area of palpebral aperture, action of toxic topical agents such as preservatives and complication in the tear film compartments. The lack of tear in the ocular surface may cause discomfort and dryness sensation [7,8,9]
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