Preparation of the multifunctional excipient ε-polylysine-protocatechuic acid and its application in eye drops

Abstract

The objective of this work was to prepare an ophthalmic excipient with antibacterial, antioxidant, and anti-inflammatory functions, which was combined with berberine hydrochloride (BBR) for the treatment of dry eye syndrome.

Protocatechuic acid-grafted-ε-polylysine (ε-PL-PA) was prepared by the carbodiimide coupling method. The degree of substitution of ε-PL-PA and the combination proportion of ε-PL-PA and BBR were screened and determined through in vitro antibacterial experiments and free radical scavenging experiments. The results of corneal permeation and eye tissue distribution experiments showed that ε-PL-PA could enhance the corneal permeation of BBR and prolong the residence time of BBR in the eyes.

The results of schirmer I test, tear break-up time test, tear ferning test, fluorescein staining test, assessment of vitamin D levels in the ocular tissues, and histopathological examination indicated that ε-PL-PA/BBR had a good effect in repairing corneal and conjunctival damage, improving the mucin and inorganic salt components of tears, reducing the pro-inflammatory factor IL-1β in the cornea, and enhancing the vitamin D level in the eyes, which were comparable to that of commercially available Ciclosporin A.

The combination of ε-PL-PA and BBR exhibited a synergistic effect in terms of antioxidant, antibacterial, and anti-inflammatory effects, as well as in the treatment of dry eye syndrome. This study provides a new idea for the development of ophthalmic antibacterial agents with high efficiency and low toxicity, and has important application prospects in the treatment of ocular surface diseases such as DES.

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Materials

ε-Polylysine, protocatechuic acid, and berberine hydrochloride were purchased from Macklin (Shanghai, China). Sodium fluorescein was acquired from Dalian Meilun Biotechnology Co., Ltd. Benzalkonium chloride was sourced from Alading (Shanghai, China). The rat vitamin D ELISA kit was sourced from Shanghai Youxuan Biotechnology Co., Ltd. All other solvents and reagents utilized in this study were of analytical-grade.

Guangjie Wang, Lidan Zhang, Changshan Sun, Tongying Jiang, Preparation of the multifunctional excipient ε-polylysine-protocatechuic acid and its application in eye drops, Journal of Drug Delivery Science and Technology, Volume 119, 2026, 108170, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2026.108170.

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