title: A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye.
abstract: OBJECTIVE
  Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease.
  
  
  METHODS
  Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye. Cs dissolved in SFA (perfluorobutylpentane = F4H5with 0.5% Ethanol), F4H5 with 0.5% ethanol only, 0.05% Cs (Restasis®), and dexamethasone (Monodex®) were applied three times daily beginning either at day 4 or day 11 of desiccating stress for up to 3 weeks after end of dry-eye induction.
  
  
  RESULTS
  In comparison to other groups, Cs/F4H5 demonstrated high efficacy and earlier reduction of corneal staining. In this study, Cs/F4H5 had the ability to maintain conjunctival goblet cell density once applied on day 4. Flow cytometry analysis from cervical lymphnodes demonstrated a significantly lower CD4+ and CD8+ T-cells in the Cs/F4H5 group following 3 weeks of therapy than at baseline, but no difference in regulatory T cells from regional lymphnodes were seen.
  
  
  CONCLUSIONS
  Overall, compared to a commercially available Cs formulation (Restasis®) and dexamethasone, Cs/F4H5 was shown to be equally effective but with a significantly faster therapeutic response in reducing signs of dry-eye disease in an experimental mouse model.
authors.affiliation: Department of Ophthalmology, Medical Faculty, University of Cologne, Kerpenerstrasse 62, 50937, Cologne, Germany.|Cluster of Excellence: Cellular Stress Response in Aging-Associated Diseases (CECAD), University Cologne, Cologne, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Gehlsen
authors.affiliation: Department of Ophthalmology, Medical Faculty, University of Cologne, Kerpenerstrasse 62, 50937, Cologne, Germany.|Cluster of Excellence: Cellular Stress Response in Aging-Associated Diseases (CECAD), University Cologne, Cologne, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Braun
authors.affiliation: Department of Ophthalmology, Medical Faculty, University of Cologne, Kerpenerstrasse 62, 50937, Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Notara
authors.affiliation: Novaliq GmbH, Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Krösser
authors.affiliation: Department of Ophthalmology, Medical Faculty, University of Cologne, Kerpenerstrasse 62, 50937, Cologne, Germany. philipp.steven@uk-koeln.de.|Cluster of Excellence: Cellular Stress Response in Aging-Associated Diseases (CECAD), University Cologne, Cologne, Germany. philipp.steven@uk-koeln.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Steven
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002452:Cell Count; D003228:Conjunctiva / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D005434:Flow Cytometry; D005466:Fluorocarbons; D005938:Glucocorticoids / Q000008:administration & dosage; D020397:Goblet Cells / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D005466:Fluorocarbons; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; C533290:perfluorobutylpentane; D003907:Dexamethasone; D016572:Cyclosporine
keywords: Cyclosporine; Desiccating stress; Dry-eye disease; Mouse model