Preliminary Studies Of Liposomal Formulation Containing An Omega-3 Fatty Acid For Dry Eye Therapy

Abstract

Purpose: Dry Eye is a highly frequent disease affecting the ocular surface. Artificial tears are directed to minimize signs and symptoms. Nevertheless the underlying inflammation is not effectively treated and simultaneous antiinflammatory therapy is usually required. It has been shown that omega (ω)-3 fatty acids have anti-inflammatory properties and they have successfully employed in dry eye therapy. The aim of this work was to develop and characterize a formulation with tear film characteristics based on ω-3 fatty acid containing liposomes for dry eye disease treatment.

Methods: Liposomes were prepared by organic solvent evaporation technique which had been modified by our research group. Briefly, a ω-3 fatty acid is incorporated with the lipid components (phosphatidylcholine, cholesterol and α-tocopherol) of liposomal vesicles in a ratio 10:0.6 (phosphatidylcholine: ω-3 fatty acid). Hypotonic aqueous solution containing trehalose is employed to disperse liposomes. Finally, a bioadhesive polymer, hyaluronic acid 0.2%, was also added. Formulation was analyzed in terms of size, pH and osmolarity. Tolerance studies were performed in vitro on a human corneal cell line (Human Inmortalized-Limbal Epithelial Cells; HCLE) based on the MTT method. Liposomal formulation was exposed to corneal cells for 15 minutes (short term exposures) and 1 and 4 hours (simulating chronic treatments).

Results: ω-3 fatty acid-loaded liposomes resulted in a size of 115.1±8.8 nm (unimodal size distribution). The liposomal formulation containing the ω-3 fatty acid showed a neutral pH. The formulation was hypotonic and resulted in 207.4±1.3 mOsm. Viability values were higher than 80% in the human corneal cell line at the three different time points studied.

Conclusions: This liposomal formulation containing the ω-3 fatty acid was suitable for topical ophthalmic application. Further studies are required to analyze the antiinflammatory effects of the formulation on the ocular surface for dry eye therapy.

Keywords: 486 cornea: tears/tear film/dry eye • 583 lipids