Topical Kojic Acid Liposomes for Alkali-Induced Corneal Injury: Comparative Study of Uncoated vs. Hyaluronic Acid-Coated Formulations in Corneal Epithelial Repair

Corneal chemical injuries are ocular emergencies that can progress to severe ulceration, scarring, and vision loss. This study evaluated topically delivered kojic acid (KA) an agent known for cell proliferation and anti-inflammatory properties in an alkali-induced corneal injury model.Uncoated liposomes and HA coated liposomes were investigated to deliver KA in the corneal tissue. Small (∼200 nm; SL-KA, SL-KA-HA) and large (∼500 nm; LL-KA, LL-KA-HA) liposomes and HA coated liposomes were formulated. Larger liposomes either coated or uncoated exhibited superior ex vivo corneal retention compared to smaller nanocarriers, with uncoated large liposomes (LL-KA: 0.613 ± 0.02 µg) achieving higher retention than HA-coated liposomes (LL-KA-HA: 0.372 ± 0.04 µg).In a 21-day rabbit model of alkali-induced corneal injury, untreated controls showed persistent inflammation and cellular adhesion, whereas free KA failed to alleviate necrosis. Conversely, LL-KA and LL-KA-HA significantly enhanced structural healing, preserved intact epithelia, and reduced stromal alterations, with superior tissue recovery in the LL-KA group. HA solution controls preserved the epithelium but failed to resolve underlying stromal inflammation. Immunohistochemistry demonstrated a marked reduction in NF-κB expression in liposome-treated groups compared to untreated, free KA, or HA controls.Liposomal delivery of KA offers a promising non-surgical therapy for alkali-induced corneal injuries, with uncoated large liposomes emerged better corneal healing.