Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac

Abstract

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti‐inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α ‐, β ‐, γ ‐, and HP‐ β ‐CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo‐, α ‐, β ‐, γ ‐, and HP‐ β ‐CD inclusion complexes were prepared and characterized and Diclo‐CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest‐ (Diclo‐) host (CD) solid inclusion complexes were formed only with β ‐, γ ‐, and HP‐ β ‐CDs. Amphipathic properties for Diclo were recorded and this surfactant‐like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo‐CDs in solution. Reduction of ocular toxicity 3‐fold to16‐fold and comparable corneal permeability to free Diclo were recorded only with Diclo‐ γ ‐CD and Diclo‐HP‐ β ‐CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo‐ γ ‐CD and Diclo‐HP‐ β ‐CD demonstrated fast healing without scar formation.