title: Thermosensitive hexanoyl glycol chitosan-based ocular delivery system for glaucoma therapy.
abstract: Conventional eye drops quickly move away from the surface of the eye; as a result, ocular bioavailability is very limited. To overcome this issue, we developed a thermosensitive hexanoyl glycol chitosan (HGC) as a carrier for topical drug delivery to the eye. Here, we modulated the degree of N-hexanoylation to control the thermogelling behavior and prepared a new ocular formulation of HGC for glaucoma therapy. The viscosity of the aqueous formulation sharply and significantly increases at body temperature. The results from cytotoxicity evaluation showed that HGC is non-toxic at up to 1.25wt.%. In vivo experiments demonstrated that HGC is maintained on the preocular surface for a comparatively longer period of time due to its enhanced viscosity at body temperature. As a result, when brimonidine was loaded, the formulation exhibited attractive bioavailability properties as well as more prolonged period of lowered intra-ocular pressure (14h) compared with Alphagan P, the marketed medication for brimonidine treatment.
  
  
  
  In this manuscript, hexanoyl glycol chitosan (HGC) was synthesized by the N-hexanoylation of glycol chitosan. We have observed that an aqueous solution of HGC exhibited a dramatic increase in viscosity as the temperature increased. The HGC-based formulation showed prolonged retention on the preocular surface and enhanced drug availability and efficacy.
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Ik Sung
authors.initials: IS
authors.lastname: Cho
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: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Beom Kang
authors.initials: BK
authors.lastname: Huh
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea; Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon 341-114, Republic of Korea.
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Cho
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Zehedina
authors.initials: Z
authors.lastname: Khatun
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea; College of Chemical Engineering and Materials Science, Tianjin University of Science & Technology, Tianjin 300-457, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon 341-114, Republic of Korea; Human and Environmental Toxicology Program, University of Science and Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
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
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: khuh@cnu.ac.kr.
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000068438:Brimonidine Tartrate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D006018:Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006358:Hot Temperature; D008297:Male; D011817:Rabbits
chemical_list: D003692:Delayed-Action Preparations; D006018:Glycols; D000068438:Brimonidine Tartrate
keywords: Glaucoma therapy; Hexanoyl glycol chitosan; Ocular delivery; Thermosensitive property