title: Dexamethasone eye drops containing γ-cyclodextrin-based nanogels.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Moya-Ortega
authors.forename: Tiago F G
authors.initials: TF
authors.lastname: Alves
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
authors.forename: Einar
authors.initials: E
authors.lastname: Stefánsson
authors.forename: Margrét
authors.initials: M
authors.lastname: Thorsteinsdóttir
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001082:Aqueous Humor / Q000378:metabolism; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D004655:Emulsions; D005782:Gels; D009883:Ophthalmic Solutions; D011817:Rabbits; D012995:Solubility; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D005782:Gels; D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003907:Dexamethasone