Abstract
The prevalence of dry eye disease (DED) is rising globally, increasingly affecting young adults. Although artificial tears are commonly used, unfortunately they do not address the inflammatory component of the disease. For this reason, in patients whose symptoms persist despite the use of artificial tears, anti-inflammatory agents such as the immunosuppressant cyclosporine A (CyA) are clinically indicated to reduce the underlying inflammation in DED. In this study, a CyA-loaded liposomal formulations composed of analogous components to the lipid and aqueous layers of the natural tears (CyA-lipo) and dispersed in an aqueous solution of sodium hyaluronate (CyA-lipo-NaHa) has been developed. Formulations were analysed for physicochemical properties, and in vitro tolerance using human corneal and conjunctival cell lines over a short-term stability study at 25 °C and 2–8 °C. In vivo tolerance was assessed in rabbits, and therapeutic efficacy was evaluated in dogs diagnosed with DED. Average vesicles’ size resulted in 204.2 ± 4.3 nm and 198.7 ± 6.0 nm for CyA-lipo and CyA-lipo-NaHa respectively. Both formulations rendered osmolarity values close to 200 mOsm and surface tension values below 31 mN/m. The addition of sodium hyaluronate produced an increase of viscosity with values of 6.030 ± 0.316 mPa·s for CyA-lipo-NaHa and 0.950 ± 0.073mPa·s for CyA-lipo. Cell viability was above 80% in corneal and conjunctival cells, and no signs of ocular surface damage in rabbit were observed. In dogs, ocular surface parameters, Schirmer’s test values in particular, improved significantly after two months of treatment (< 13 mm/min before and higher than15 mm/min in all animals after treatment). This liposomal formulation demonstrates optimal physicochemical properties, biocompatibility, and therapeutic efficacy, supporting its potential as an optimised treatment for DED. GRAPHICAL ABSTRACT: [Image: see text]