Hydrophilic acrylic hydrogels with built-in or pendant cyclodextrins for delivery of anti-glaucoma drugs

Carbonic anhydrase inhibitors (CAIs) are gaining interest for local treatment of glaucoma and other ocular disorders. The aim of this work was to elucidate the role of cyclodextrins (CDs) in the loading and the release rate of acetazolamide (ACT) and ethoxzolamide (ETOX) from N,N-dimethylacrylamide-co-N-vinylpyrrolidone (DMA-co-NVP) hydrogels, suitable as high water-content soft contact lenses. Two different approaches to incorporate the CDs were evaluated: (i) synthesis of CD monomers and copolymerization with DMA and NVP; and (ii) grafting of natural CDs to preformed hydrogels. Natural β-CD and γ-CD were tested in each approach. The effects of the preparation method on relevant functional features of the hydrogels as well as on cytocompatibility and drug delivery performance were studied in detail. The role played by the CDs strongly depends on the physicochemical properties of the drug and its ability to form complexes; being particularly relevant for slightly soluble molecules that have high affinity for the CDs. Otherwise, unspecific interactions with the network may screen the contribution of the CDs.