The crying game: lipid-based ophthalmic nanomedicines, and in vitro models to test their performance against dry eye disease

Dry eye disease (DED), the most prevalent ocular surface disorder worldwide, is currently treated with topical formulations for hydration, lubrication, or anti-inflammatory action. Due to natural barriers of the ocular surface, which limit retention and penetration of exogenous materials, the local bioavailability of topical formulations is minimal. Lipid-based nanomedicines are the most accepted nanomedicines by the pharmaceutical industry and regulatory agencies. Evaporative DED cases could benefit from topical mucoadhesive or mucopenetrating lipid-based ophthalmic nanomedicines (LBON). Besides lubricating and restoring the lipid film, topical nanomedicines offer site-specific drug delivery, magnified targeted intracellular delivery, and reduced systemic drug distribution. The resultant reduced dosing frequency may improve patients' adherence to chronic treatments. To treat DED, however, LBON must not interfere with vision or irritate, and their chemical composition, osmolarity, viscosity, pH, and refractive index must be properly selected/adjusted. Importantly, pharmacokinetics and pharmacodynamics of nanomedicines depend on the techniques used to produce each nanoparticulate structure. Hence, the structural features and resultant activities of nanomedicines prepared at lab scale, differ from those being manufactured at larger industrial scales. Due to ethical and economic reasons, preclinical assessment of LBON should therefore be performed using in vitro disease models. Here, the preclinical performances of LBON reported over the past 10 years, are critically examined. Overall, to become more significant and predictable, further preclinical developments of LBON need to become more technically rigorous and include the help of more sophisticated and broadly available in vitro models.