Cyclosporine-loaded cross-linked inserts of sodium hyaluronan and hydroxypropyl-beta-cyclodextrin for ocular administration

This work aimed to develop cyclosporine ocular inserts combining sodium hyaluronate (HA) and hydroxypropyl-beta-cyclodextrin (HP beta CD). Four different formulations, cross-linked with poly(ethylene glycol) diglycidyl ether, were studied to elucidate the role of the HA:HP beta CD proportion on the physical characteristics and drug release patterns. The inserts (300 mu m thickness) showed porous surfaces, high swelling ratios (similar to 10), and good cyto-compatibility with fibroblasts and chorioallantoic membrane (HET-CAM test). Cyclosporine-loaded inserts (similar to 0.5% w/w drug content) appeared translucent. Release tests carried out under continuous flow of simulated lacrimal fluid revealed a controlled release of cyclosporine during the first 1 h. Conversely, differences among formulations were evidenced when the inserts were immersed in plenty volume of fluid; inserts with low content in HP beta CD released the drug faster. These later inserts also facilitated cyclosporine accumulation into sclera (5.6-32.7 mu g(drug)/g(sclera)). Thus, cross-linked HA:HP beta CD inserts appear as a suitable platform for peptide drug release to the ocular surface.