Nanogels (NGs) are currently under extensive investigation due to their unique properties, such as small particle size, high encapsulation efficiency and protection of active agents from degradation, which make them ideal candidates as drug delivery systems (DDS). Stimuli-responsive NGs are cross-linked nanoparticles (NPs), composed of polymers, natural, synthetic, or a combination thereof that can swell by absorption (uptake) of large amounts of solvent, but not dissolve due to the constituent structure of the polymeric network. NGs can undergo change from a polymeric solution (swell form) to a hard particle (collapsed form) in response to (i) physical stimuli such as temperature, ionic strength, magnetic or electric fields; (ii) chemical stimuli such as pH, ions, specific molecules or (iii) biochemical stimuli such as enzymatic substrates or affinity ligands. The interest in NGs comes from their multi-stimuli nature involving reversible phase transitions in response to changes in the external media in a faster way than macroscopic gels or hydrogels due to their nanometric size. NGs have a porous structure able to encapsulate small molecules such as drugs and genes, then releasing them by changing their volume when external stimuli are applied.

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.