Rebamipide liposome as an effective ocular delivery system for the management of dry eye disease

Dry eye disease (DED) is a public health concern that cause ocular discomfort and visual disturbance, which seriously affect quality of life. Rebamipide (RBM) is one of the drugs used for DED treatment, the ophthalmic RBM suspension (Mucosta®) has been used to treat DED in Japan. However, due to the drug removing through the nasolacrimal duct, the residence time of suspension on the ocular surface is short. RBM in excess of the therapeutic dose irritate the ocular surface and cause more tear production. Moreover, the opaque and turbid appearance of the suspension can lead to blurred vision after administration. In this study, we designed RBM liposomal eye drops for the treatment of DED, which have great stability, good patient compliance and a slow-release rate. RBM liposomes were prepared by remote loading technique and optimized for different formulation parameters. The appropriate HSPC-to-Chol ratio, drug-to-lipid ratio, calcium acetate solution concentration, incubation time and temperature were selected according to the encapsulation efficacy of RBM liposomes. The encapsulation efficacy and in vitro release of RBM were evaluated. The retention, tolerability and therapeutic effect of RBM liposomes were evaluated in rats. The ocular distribution of RBM was evaluated in vivo in rabbits’ eyes. The retention time of RBM liposomes in the cornea is longer than that of suspensions. While reducing the drug dose and irritation to ocular surface, RBM liposomes maintain the same efficacy and increase the concentration in cornea and aqueous humor. RBM liposomes suggested a further application in ophthalmic therapy, especially for DED.