Absorption enhancement strategies in chitosan-based nanosystems and hydrogels intended for ocular delivery: Latest advances for optimization of drug permeation

Ophthalmic diseases can be presented as acute diseases like allergies, ocular infections, etc., or chronic ones that can be manifested as a result of systemic disorders, like diabetes mellitus, thyroid, rheumatic disorders, and others. Chitosan (CS) and its derivatives have been widely investigated as nanocarriers in the delivery of drugs, genes, and many biological products. The biocompatibility and biodegradability of CS made it a good candidate for ocular delivery of many ingredients, including immunomodulating agents, antibiotics, ocular hypertension medications, etc. CS-based nanosystems have been successfully reported to modulate ocular diseases by penetrating biological ocular barriers and targeting and controlling drug release. This review provides guidance to drug delivery formulators on the most recently published strategies that can enhance drug permeation to the ocular tissues in CS-based nanosystems, thus improving therapeutic effects through enhancing drug bioavailability. This review will highlight the main ocular barriers to drug delivery observed in the nano-delivery system. In addition, the CS physicochemical properties that contribute to formulation aspects are discussed. It also categorized the permeation enhancement strategies that can be optimized in CS-based nanosystems into four aspects: CS-related physicochemical properties, formulation components, fabrication conditions, and adopting a novel delivery system like implants, inserts, etc. as described in the published literature within the last ten years. Finally, challenges encountered in CS-based nanosystems and future perspectives are mentioned.