Alginate-functionalized nanoceria as ion-responsive eye drop formulation to treat corneal abrasion

In this study, we aimed to develop ion-responsive and biocompatible alginate-capped nanoceria (Ce-ALG) for β-1,3-glucan (i.e., wound healing agent) delivery and corneal abrasion (CA) treatment. Specifically, alginate coatings confer the metallic nanocarriers with enhanced mucoadhesion, prolonged precorneal retention via hydrogen bonding, and improved viscosity. Additionally, increasing alginate grafting amount increased the surface stiffness and facilitated cellular uptake, thereby increasing bioactive potential of the nanocarriers. On the other hand, a stable egg-box structure formed by alginate complexation with Ca²⁺ not only heightened the encapsulation efficiency of β-1,3-glucan, but also provided sustained drug release during ion exchange with Na⁺ in tears. In vitro studies demonstrated an improvement in pharmacological wound closure, as evidenced by the accelerated migration and proliferation of corneal epithelial cells exposed to β-1,3-glucan-loaded Ce-ALG. In a rabbit model of CA, a single dose of the eye drop formulation with the maximum grafting amount of alginate remarkably reduced epithelial injury area by ~99 % at 5 days post-instillation, which was 45- and 53-fold more effective in wound area reduction than that of Ce and ketorolac (an analgesic commonly used for managing CA) groups, respectively. Overall, surface functionalization with alginate greatly enhanced the ocular bioavailability of nanotherapeutics for corneal epithelial injury recovery.