title: Enhanced ocular efficacy of topically-delivered dorzolamide with nanostructured mucoadhesive microparticles.
abstract: Dorzolamide eye drops are widely prescribed to reduce intraocular pressure (IOP) in the treatment of ocular hypertension and glaucoma. However, in an eye drop formulation, dorzolamide is rapidly cleared from the preocular space, hence requiring multiple daily administrations. Here, we sought to increase the preocular retention of dorzolamide using nanostructured, mucoadhesive microparticles (MUCO_NM) as carriers for topical delivery to the eye. MUCO_NM were prepared by freeze-milling dorzolamide-loaded, electrospun nanofibers composed of poly(lactic-co-glycolic acid) and polyethylene glycol. The microparticles were embedded in a rapidly-dissolving tablet of polyvinyl alcohol. To assess in vivo efficacy, the MUCO_NM were administered topically to the eyes of rabbits, and IOP was measured and compared to that in eyes treated with Trusopt®, a marketed eye drop of dorzolamide. The MUCO_NM showed a 35% greater maximum IOP decrease and a>2-fold increase in the duration of the IOP decrease, compared to Trusopt®. This enhanced efficacy was comparable to that obtained with a single administration of 4 drops of Trusopt®or 2 administrations of Trusopt®at a 4-h interval. Our findings suggest that this MUCO_NM preparation is a promising carrier for topical delivery of dorzolamide to the eye, with enhanced drug efficacy and the potential to reduce administration frequency.
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; Department of Ophthalmology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Young Kook
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Se-Na
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Beom Kang
authors.initials: BK
authors.lastname: Huh
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Hyein
authors.initials: H
authors.lastname: Won
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; Department of Ophthalmology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea; Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, 08826, Republic of Korea; Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D000269:Adhesives; D060433:Administration, Ophthalmic; D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004339:Drug Compounding; D007429:Intraocular Pressure / Q000187:drug effects; D019344:Lactic Acid; D008297:Male; D009092:Mucous Membrane; D057139:Nanofibers; D009883:Ophthalmic Solutions; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019946:Propylene Glycol; D011817:Rabbits; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000269:Adhesives; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019946:Propylene Glycol; C062765:dorzolamide
keywords: Dorzolamide; Glaucoma; Intraocular pressure; Microparticles; Mucoadhesion; Nanostructures