Effects of eye drops containing hyaluronic acid-nimesulide conjugates in a benzalkonium chloride-induced experimental dry eye rabbit model

Tzu Yang Chen, Ching Li Tseng, Chih An Lin, Hua Yang Lin, Parthiban Venkatesan, Ping Shan Lai

Research output: Contribution to journalArticlepeer-review

Abstract

Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflam-matory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioa-vailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompati-bility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis®, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Im-portantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical applica-tion. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E2 (PGE2) in the lipopolysaccharide (LPS)-stimu-lated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES.

Original languageEnglish
Article number1366
JournalPharmaceutics
Volume13
Issue number9
DOIs
Publication statusPublished - 2021

Keywords

  • Anti-inflammatory
  • COX-2 inhibitor
  • Ocular
  • Solvent-free
  • Topical administration

ASJC Scopus subject areas

  • Pharmaceutical Science

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