Covalently Cross-Linked Chitosan Hydrogel Sheet for Topical Ophthalmic Delivery of Levofloxacin

In the present study, a covalently cross-linked chitosan hydrogel sheet was fabricated and assessed as an ophthalmic carrier for topical delivery of levofloxacin. Upon mixing 4-arm polyethylene glycol with aldehyde end groups (4-arm PEG-CHO) with glycol chitosan (GC) at various feed ratios, a series of hydrogel sheets formed spontaneously under mild conditions. Rheological characterization illustrated that the gelation time and moduli of the hydrogels could be tuned by controlling the component concentrations. The swelling ratio of hydrogels increased with decreasing 4-arm PEG-CHO and GC concentrations. The proposed hydrogel exhibited a typical porous structure, with pore size in the range 20-150 μm. This structure allowed the encapsulated levofloxacin to be released from the hydrogel matrix via diffusion within the first 0.5 h, followed by a sustained release up to 24 h. In vitro cytotoxicity and biocompatibility assays showed that the proposed hydrogels are relatively noncytotoxic and have excellent cytocompatibility with L-929 cells after 24 h of incubation. Furthermore, an ocular irritation test demonstrated the non-irritant character of the proposed hydrogel after topical application. These characteristics support the potential use of covalently cross-linked chitosan hydrogel sheets in topical ophthalmic drug delivery applications.