title: Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery system for glaucoma.
abstract: OBJECTIVE
  We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS).
  
  
  METHODS
  We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 μg/cm(2) LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits.
  
  
  RESULTS
  The 0.25 μg/cm(2) LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 μg/cm(2) LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% ± 14.8%, -22.0% ± 16.7%, -25.8% ± 18.0%, -22.7% ± 20.9%, and -6.6% ± 17.0%, respectively. The 25 μg/cm(2) LBNS reduced IOP in a similar manner. The 25 μg/cm(2) LBNS induced transient hyperemia, whereas the 0.25 and 2.5 μg/cm(2) LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 μg/cm(2) LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 μg/cm(2) LBNS.
  
  
  CONCLUSIONS
  LBNS may be used as a novel antiglaucoma DDS.
authors.affiliation: Department of Ophthalmology, University of Yamanashi Faculty of Medicine, Chuo, Yamanashi, Japan. kenjik@yamanashi.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Haniuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohtsubo
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
mesh_terms: D020341:Absorbable Implants; D000464:Alginates / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001522:Behavior, Animal; D048271:Chitosan / Q000008:administration & dosage / Q000009:adverse effects; D003315:Cornea / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005901:Glaucoma / Q000188:drug therapy*; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000009:adverse effects; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D049329:Nanostructures / Q000008:administration & dosage* / Q000009:adverse effects; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000464:Alginates; D000959:Antihypertensive Agents; D006603:Hexuronic Acids; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D020723:Glucuronic Acid; D048271:Chitosan
keywords: chitosan; drug delivery system; glaucoma; latanoprost; nanosheet; sodium alginate