title: Mucoadhesive microparticles with a nanostructured surface for enhanced bioavailability of glaucoma drug.
abstract: Topical drug administration to the eye is limited by low drug bioavailability due to its rapid clearance from the preocular surface. Thus, multiple daily administrations are often needed, but patient compliance is low, hence a high chance of unsatisfactory treatment of ocular diseases. To resolve this, we propose mucoadhesive microparticles with a nanostructured surface as potential carriers for delivery of brimonidine, an ocular drug for glaucoma treatment. For sustained drug delivery, the microparticles were composed mainly of a diffusion-wall material, poly(lactic-co-glycolic acid) and a mucoadhesive polymer, polyethylene glycol, was used as an additive. Due to their nanostructured surface, the microparticles with a mucoadhesive material exhibited a 13-fold increase in specific surface area and could thus adhere better to the mucous layer on the eye, as compared with the conventional spherical microparticles. When loaded with brimonidine, the mucoadhesive microparticles with a nanostructured surface increased both drug bioavailability and its activity period by a factor of more than 2 over Alphagan P, a marketed eye drop of brimonidine.
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Young Kook
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Mi Jeung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, 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 152-742, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: You Jung
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Jung
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: kihopark@snu.ac.kr.
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea; Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea; Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D000268:Adhesiveness; D060433:Administration, Ophthalmic; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D000068438:Brimonidine Tartrate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D005901:Glaucoma / Q000188:drug therapy*; D008297:Male; D009093:Mucus / Q000378:metabolism; D053758:Nanoparticles; D036103:Nanotechnology; D009883:Ophthalmic Solutions; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011098:Polyglactin 910 / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011817:Rabbits; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D004337:Drug Carriers; D009883:Ophthalmic Solutions; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D000068438:Brimonidine Tartrate
keywords: Drug delivery; Glaucoma; Microparticles; Mucosal adhesion; Nanostructured surface; Ophthalmology