Ocular topical application of alpha-glucosyl hesperidin as an active pharmaceutical excipient: in vitro and in vivo experimental evaluation

Alpha-glucosyl hesperidin (GH) is an aqueous soluble, amphipathic hesperidin derivative with several pharmacological effects, and it is postulated in this manuscript that GH could potentially be utilized as an active pharmaceutical excipient in eyedrops. The ocular safety of GH was evaluated according to in vitro cytotoxicity and in vivo ocular tolerance. The in vivo corneal permeation of coumarin-6 (Cou-6) with or without GH was characterized, and the in vivo inducing corneal wound healing using bisdemethoxycurcumin (BDMC) with or without GH was also evaluated to determine whether GH is an active pharmaceutical excipient in eyedrops. The results demonstrated that as high as 30 mg/ml of GH exhibits high-level in vitro and in vivo safety profiles according to four in vitro and in vivo evaluations. GH improved the corneal permeation of Cou-6 in mice, as well as demonstrated in vitro antioxidant activity. Concerning in vivo activity, a BDMC–GH suspension was shown to be synergistic in promoting corneal wound healing in mice, as well as restoring corneal sensitivity, promoting corneal epithelial wound healing, and restoring the corneal tissue structure without inflammatory cell infiltration. Overall, GH could be a novel and promising active excipient in eyedrops. Graphical Abstract