title: Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy.
abstract: Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucoma with increased bioavailability and improved compliance. Contact lenses are developed for extended simultaneous release of timolol and dorzolamide, both of which are commonly prescribed hydrophilic drugs. The extended release is achieved by loading lenses with vitamin E barriers. In vitro release studies are performed with control and vitamin E loaded lenses for both drugs loaded separately and then together in the same lens. The safety and efficacy of combination therapy by contacts are demonstrated in a Beagle model of glaucoma. Simultaneous loading of timolol and dorzolamide increases the release duration of both drugs. Also vitamin E incorporation is highly effective in increasing the release durations of both drugs to about 2-days. The lenses loaded with both drugs exhibited superior IOP reduction compared to eye drops with about 6-fold lower drug loading. More importantly, combination therapy by continuous wear of vitamin E loaded contact for 2-days, followed by a new set of contacts for another two days, reduced IOP during the 4days of wear time and for another 8days after removal of the contacts. Vitamin E loading is very effective for providing combination therapy by contact lenses due to the increase in release durations of several drugs. The contact lens based therapy reduces IOP with lower drug dose compared to eye drops and may significantly improve the compliance as the effect of the therapy lasts significantly longer than the wear-duration.
authors.affiliation: Department of Chemical Engineering, University of Florida, PO Box 116005, Gainesville, FL 32611-6005, United States. Electronic address: vansin@ufl.edu.
authors.forename: Kuan-Hui
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: College of Veterinary Medicine, University of Florida, PO Box 100101, Gainesville, FL 32610, United States. Electronic address: becarbia@ufl.edu.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Carbia
authors.affiliation: College of Veterinary Medicine, University of Florida, PO Box 100101, Gainesville, FL 32610, United States. Electronic address: plummerc@ufl.edu.
authors.forename: Caryn
authors.initials: C
authors.lastname: Plummer
authors.affiliation: Department of Chemical Engineering, University of Florida, PO Box 116005, Gainesville, FL 32611-6005, United States. Electronic address: Chauhan@che.ufl.edu.
authors.forename: Anuj
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003261:Contact Lenses; D003692:Delayed-Action Preparations; D004285:Dogs; D065546:Drug Liberation; D004359:Drug Therapy, Combination; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D009883:Ophthalmic Solutions; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014810:Vitamin E / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D014810:Vitamin E; D013999:Timolol; C062765:dorzolamide
keywords: Combination therapy; Contact lenses; Dorzolamide; Glaucoma; Timolol; Vitamin E