Novel Nano-Liposome Formulation for Dry Eyes with Components Similar to the Preocular Tear Film.

Marta Vicario-De-La-Torre,Rocío Herrero-Vanrell,Beatriz De Las Heras,Eva Vico,Laura Morales-Fernández,Irene Molina-Martínez,María Caballo-González,Pedro Arriola-Villalobos,José Benítez-Del-Castillo,Manuel Guzmán,Thomas Millar

doi:10.3390/polym10040425

Abstract

Dry eye is commonly treated with artificial tears; however, developing artificial tears similar to natural tears is difficult due to the complex nature of tears. We characterized and evaluated a novel artificial tear formulation with components similar to the lipid and aqueous constituents of natural tears. Nano-liposomes, composed in part of phosphatidylcholine, were dispersed in an aqueous solution of bioadhesive sodium hyaluronate. Liposome size, zeta potential, and physicochemical properties of the fresh and stored (4 °C) liposomal formulation were analyzed. In vitro tolerance was tested using human corneal and conjunctival cell lines by exposures of 15 min to 4 h. The tolerance of the liposomal formulation was evaluated in animals (rabbits). The average liposome size was 186.3 ± 7.0 nm, and the zeta potential was negative. The osmolarity of the formulation was 198.6 ± 1.7 mOsm, with a surface tension of 36.5 ± 0.4 mN/m and viscosity of 3.05 ± 0.02 mPa·s. Viability values in the human corneal and conjunctival cell lines were always >80%, even after liposomal formulation storage for 8 weeks. Discomfort and clinical signs after instillation in rabbit eyes were absent. The new formulation, based on phosphatidylcholine-liposomes dispersed in sodium hyaluronate has suitable components and characteristics, including high in vitro cell viability and good in vivo tolerance, to serve as a tear substitute.

Highlights

Dry eye disease (DED) is a multifactorial syndrome involving alterations of the preocular tear film and ocular surface tissues that result in symptoms such as discomfort, visual disturbance, tear film instability, and inflammation [1,2]
Observations were made prior to the first instillation and at 3, 6, and 24 h afterwards; * highest score recorded for the three evaluation periods. These initial studies demonstrate that a formulation based on different components of the tear film is likely to be useful for the treatment of DED, a condition that affects 14–33% of the population [36]
Besides being non-toxic to the ocular surface, formulations need to achieve the pharmaceutical requirements described in the pharmacopoeia [37]

Summary

Introduction

Dry eye disease (DED) is a multifactorial syndrome involving alterations of the preocular tear film and ocular surface tissues that result in symptoms such as discomfort, visual disturbance, tear film instability, and inflammation [1,2]. The preocular tear film is a complex and dynamic structure formed by lipid and aqueous components (Figure 1). The aqueous phase is covered by a lipid layer that facilitates spreading and stability of the preocular tear film [4,5], and it resists collapse of the film [6]. The lipid phase is composed of two fractions: an outer non-polar one at the air interface and an inner polar component in contact with the aqueous-mucin layer. The polar amphiphilic lipids are mainly phospholipids, glycosphingolipids, and ceramides. Phospholipids comprise 5–15% of the total lipid fraction, and the main component, phosphatidylcholine, is close to 40% of the total polar lipids [7,8,9,10,11]

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Conclusion