Multifunctional anionic nanoemulsion with linseed oil and lecithin: a preliminary approach for dry eye disease.

Abstract

The treatment of dry eye disease (DED) often requires frequent use of artificial tear products. Because of their low permeability and limited ocular bioavailability, repeated applications are required for therapeutic effectiveness. In contrast to traditional drug delivery systems (DDS), a functional ophthalmic nanoemulsion was specifically designed to alleviate symptoms of DED by leveraging its antioxidant and osmoprotective properties. The study evaluated the optimal concentration of lecithin required to produce nanoemulsions with a uniform particle size and incorporated a co-surfactant to enhance the stability of the nanoformulation. A straightforward method was proposed, involving the dilution of the preformulation in an ophthalmic vehicle, followed by homogenization through ultrasonication, resulting in OphtNE-3.70% with a droplet diameter of 173 nm and a zeta potential of -44.7 mV. The addition of Kolliphor^® HS15 in OphtNE-3.66%(K1%) initially reduced the droplet size to 70.8 nm and enhanced the antioxidant effect. Although the droplet size and polydispersity index increased after more than 60 days, the formulation remained physically quite stable without phase separation. Both nanoformulations contained 2.6% (w/v) linseed oil, providing a bioactive concentration compatible with ocular administration volumes (~50 µL). At a final concentration of 1.30 mg·mL^-1, OphtNE-3.66%(K1%) showed >75% cell viability in L929 cells and ~10% 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant effect. These findings support the multifunctional potential (cytocompatibility and antioxidant) of sterile OphtNE-3.66%(K1%) for the treatment of DED, emphasizing the need for in vivo studies to ensure its efficacy and safety for ocular administration.