Considerations for nanoscale drug-delivery systems for the cornea

Drug delivery in cornea remains a challenge due to its unique dome shape, anatomy, epithelial barrier, rapid drug clearance, and eyelid blinking. Nanoscale-based drug delivery systems are particularly attractive for treating corneal diseases due to sustained local drug release without major side effects. Nano drug delivery systems have potential to overcome many limitations including drug's residence-time, controlled-release, and solubility in the cornea. This review provides an overview of critical considerations for corneal nanomedicine development ranging from the nanoscale-design to achieving an optimal drug delivery with a discussion on cornea-specific biology and diseases. Herein, we discuss key anatomical features and drug transport challenges across the tear film, mucins/glycocalyx, epithelium, stroma, and endothelium that can influence nanoparticle behavior. Further, article outlines indication-driven target drug profiling; core physicochemical parameters related to drug retention, penetration, distribution, and safety; and factors affecting sterility, osmolality, tolerability, and pH, regulatory expectations, and manufacturing reproducibility. Overall, nanoscale drug delivery systems offer an attractive approach to treat corneal dysfunction without major side effects.