Objective  To prepare hyaluronic acid-rebamipide conjugate by coupling hyaluronic acid with rebamipide through ester bonds, improve the solubility of rebamipide, combine the moisturizing effect of hyaluronic acid with the promotion of mucin secretion by rebamipide, and realize collaborative treatment for dry eye syndrome.

Methods  Carbonyl diimidazole (CDI) was used to activate rebamipide, and the activated rebamipide was esterified with hyaluronic acid to obtain the hyaluronic acid-rebamipide conjugate. The structure of the conjugate was characterized by 1HNMR, IR and UV spectrophotometry. The conjugate was dissolved in water, and the content of rebamipide in the conjugate was determined by UV spectrophotometry.

Results  Hyaluronic acid-rebamipide conjugate with different rebamipide content could be obtained by adjusting rebamipide feeding ratios. When the content of rebamipide was (5.73±0.10)%, its particle size was (159.68±1.20) nm, and the Zeta potential was (-18.82±0.37) mV. When the content of rebamipide was (6.02±0.05)%, its particle size was (210.86±3.50) nm, and the Zeta potential was (-22.59±0.22) mV. As the content of rebamipide increasing, the particle size of the nanoparticles also increased. After the formation of the conjugate, the highest solubility of rebamipide in water was (0.60±0.07) mg/mL.

Conclusion  The hyaluronic acid-rebamipide conjugate prepared in this experiment can effectively improve the solubility of rebamipide in water. Conjugates with high degree of substitution can form uniformly sized nanoparticles, further expanding the application of rebamipide in ophthalmic formulations.

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