Time-sequential delivery of vitamin a palmitate and prednisolone acetate from a structurally tailored contact lens for corneal injury therapy.

The demand for corneal tissue healing and for the prevention of complications is growing. Conventional multi-drug eye drop therapy is significantly hampered by poor drug bioavailability and low patient compliance, which creates an urgent need for the development of drug co-delivery strategies. In this study, vitamin A palmitate (VAP) and prednisolone acetate (PA) were utilized to construct time-sequential drug-loaded bandage contact lenses (BCLs) to achieve the therapeutic requirements that address epithelial repair followed by stromal anti-inflammatory therapy. The solubility and drug-loading capacity of VAP and PA were enhanced by investigating cyclodextrin (CD) structures that encapsulate the two drugs. Subsequently, VAP pH-responsive films and PA sustained-release lenses were prepared separately and integrated into a "sandwich" structure. The fabricated dual-drug film BCLs achieved time-sequential delivery of VAP and PA over 144 h. In vitro release and permeation studies demonstrated the drug release behavior and release mechanisms of the film-based and BCLs-mediated drug delivery system. Comprehensive evaluations, including cytocompatibility assays, analysis of inflammatory cytokines, ocular irritation assessment, and alkali burn model studies, demonstrated the system's excellent biocompatibility, effective repair ability to promote corneal epithelial regeneration while significantly suppressing scar formation. This study not only achieved time-sequential drug release precisely tailored to the distinct healing requirements of different corneal injury stages but also elucidates the structure-release relationship of the BCLs system.