Work

In situ self-assembling rebamipide-based eye drops to promote secretion of mucin for treatment of dry eye

Year: 2026

Type: article

Abstract: Rebamipide is effective for dry eye management, but its insolubility limits formulation development. An optimal design is crucial for patient comfort and maximizing bioavailability. Here we covalently conjugate rebamipide with a peptide motif (FFFYpEH) to generate a peptide-drug conjugate that dramatically improves solubility and enables in situ self-assembly. After topical instillation, the conjugate undergoes enzyme-instructed self-assembly, leading to enhanced drug retention (>25 min) on the ocular surface. In vitro , the conjugate stimulates MUC1 secretion in human corneal epithelial cells and MUC5AC secretion in human conjunctival epithelial cells. In a murine dry eye model, the conjugate demonstrates superior therapeutic efficacy over commercial rebamipide eye drops (Mucosta®), as evidenced by significant symptom alleviation, enhanced corneal epithelial repair, restored tear secretion, and increased conjunctival goblet cell density. Relative to the 14-day non-intervention, treatment of the conjugate results in a threefold increase in corneal epithelium thickness, achieving normal levels. Tear secretion rises nearly fivefold, and conjunctival goblet cell density triples, reaching values comparable to a healthy cornea. Overall, this work addresses the limitations of existing drugs by developing a strategy that not only enhances drug solubility but also promotes ocular retention through in situ self-assembly, thereby offering a promising clinical solution for dry eye management.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2026.102899