title: Cyclosporine Amicellar delivery system for dry eyes.
abstract: BACKGROUND
  The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy.
  
  
  METHODS
  CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining.
  
  
  RESULTS
  MS-CsA had a smaller particle size (average diameter 14-18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (P<0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83±8.38, a significantly higher result than the 65.17±11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells.
  
  
  CONCLUSIONS
  The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes.
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences; College of Pharmacy, Yonsei University, Incheon, South Korea.
authors.forename: Han
authors.initials: H
authors.lastname: Kang
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Cha
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences.
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Cho
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences.
authors.forename: Junsung
authors.initials: J
authors.lastname: Park
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences; College of Pharmacy, Yonsei University, Incheon, South Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Sun
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences; College of Pharmacy, Yonsei University, Incheon, South Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Hyun
authors.affiliation: Yonsei Institute of Pharmaceutical Sciences; College of Pharmacy, Yonsei University, Incheon, South Korea.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002452:Cell Count; D048430:Cell Shape / Q000187:drug effects; D003228:Conjunctiva / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008823:Micelles; D009883:Ophthalmic Solutions / Q000494:pharmacology / Q000627:therapeutic use; D009994:Osmolar Concentration; D010316:Particle Size; D011817:Rabbits; D013666:Tears / Q000187:drug effects; D013696:Temperature; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D008823:Micelles; D009883:Ophthalmic Solutions; D016572:Cyclosporine
keywords: Cremophor EL; Restasis; cyclosporine A; dry eyes; micelle solution