A hyaluronic acid-modified cyclodextrin self-assembly system for the delivery of β-carotene in the treatment of dry eye disease

Abstract

Dry eye disease (DED) is a multifactorial ocular disease, the core mechanism of which is the tear film instability caused by ocular oxidative stress damage and inflammation. Although various pharmaceutical agents are available for DED treatment, their effectiveness is often limited by the eyes' unique biological barriers, and the long-term use of steroid hormones can lead to several adverse effects. This study reported a nano-supramolecular delivery system consisting of a polycyclodextrin (PCD), hyaluronic acid (HA) and the natural compound β-carotene (BC) for the DED treatment. Our findings indicate that the HA/PCD@BC eye drops effectively distribute on the ocular surface, retain BC, and significantly enhance the corneal penetration of BC. The excellent biocompatibility of HA/PCD@BC was demonstrated through viability testing on different cell lines, the Draize eye test, as well as the hematoxylin-eosin staining (H&E) sections of cornea and conjunctiva. Both in vitro oxidative stress assays and in vivo DED model evaluations demonstrated that the HA/PCD@BC delivery system significantly reduced abnormal oxidative stress levels on the ocular surface, inhibited the secretion of inflammatory factors, and increased the secretion of tear film stabilizing mucin. These effects collectively improved pathological changes in eye tissues and minimized damage to the ocular surface. It is of particular importance to note that HA/PCD@BC eye drops showed superior efficacy in comparison to cyclosporine A (CsA), an FDA-approved first-line drug. To sum up, the HA/PCD@BC nanodelivery system provides a natural, safe and effective therapeutic strategy for the treatment of DED and various ocular diseases.

Keywords: Dry eye disease; Hyaluronic acid; Oxidative stress; Polycyclodextrin; Solubilization; β-Carotene.