Dexamethasone Eye Drops Containing γ-cyclodextrin-based Nanogels

Sustained release aqueous eye drops of dexamethasone, based on cyclodextrin (CD) nanogels, were designed and tested in vivo. γCD units were cross-linked in the form of nanogels by means of an emulsification/solvent evaporation process. The composition of the nanogels was optimized with regard to drug loading and release rate. The eye drops consisted of an aqueous solution of dexamethasone in 2-hydroxypropyl-γ-cyclodextrin (HPγCD) medium containing γCD nanogels. The nanogel eye drops (containing 25 mg dexamethasone per ml) were tested in rabbits and compared to the commercially available product Maxidex(®) (suspension with 1 mg dexamethasone per ml). One drop administration of the nanogel eye drops resulted in nearly constant dexamethasone concentration for at least 6h in the tear fluid (mean concentration±SD=295±59 μg/ml) whereas the concentration after administration of Maxidex(®) fell rapidly from 9.72±3.45 μg/ml 1 h after application to 3.76±3.26 μg/ml 3 h after application. The maximum dexamethasone concentration in the aqueous humor (2 h after application) was 136±24 mg/ml after application of the nanogel eye drops, and only 44.4±7.8 μg/ml after application of Maxidex(®). The dexamethasone nanogel eye drops were well tolerated with no macroscopic signs of irritation, redness or other toxic effects.