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

This work aimed to develop cyclosporine ocular inserts combining sodium hyaluronate (HA) and hydroxypropyl-β-cyclodextrin (HPβCD). Four different formulations, cross-linked with poly(ethylene glycol) diglycidyl ether, were studied to elucidate the role of the HA:HPβCD proportion on the physical characteristics and drug release patterns. The inserts (300 μm thickness) showed porous surfaces, high swelling ratios (∼10), and good cytocompatibility with fibroblasts and chorioallantoic membrane (HET-CAM test). Cyclosporine-loaded inserts (∼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 HPβCD released the drug faster. These later inserts also facilitated cyclosporine accumulation into sclera (5.6-32.7 μgdrug/gsclera). Thus, cross-linked HA:HPβCD inserts appear as a suitable platform for peptide drug release to the ocular surface.