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To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs) and evaluated particle size, surface charge, and morphology. The in vitro biocompatibility of GPs was assessed using human corneal epithelium (HCE) cells and in vivo safety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+), +33 mV; size, 180.6±45.7 nm). Water-soluble tetrazolium salt (WST)-1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP-treated HCE cells. In vivo examination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+) group, and higher fluorescence intensity in the GP(+) group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+) have a great potential as vehicles for ocular drug delivery.

Cationic Gelatin Nanoparticles for Drug Delivery to the Ocular Surface: In Vitro and In Vivo Evaluation