A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye.

Abstract

PURPOSE:

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: Uta Gehlsen, Tobias Braun, Maria Notara, Sonja Krösser, Philipp Steven
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 255 Issue 4 Pg. 767-775 (Apr 2017) ISSN: 1435-702X [Electronic] Germany
• PMID: 28091781 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• Fluorocarbons
• Glucocorticoids
• Immunosuppressive Agents
• Ophthalmic Solutions
• perfluorobutylpentane
• Dexamethasone
• Cyclosporine

Topics

• Administration, Topical
• Animals
• Cell Count
• Conjunctiva (pathology)
• Cyclosporine (administration & dosage)
• Dexamethasone (administration & dosage)
• Disease Models, Animal
• Drug Carriers
• Drug Therapy, Combination
• Dry Eye Syndromes (diagnosis, drug therapy, prevention & control)
• Female
• Flow Cytometry
• Fluorocarbons
• Glucocorticoids (administration & dosage)
• Goblet Cells (pathology)
• Immunosuppressive Agents (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Ophthalmic Solutions (administration & dosage)
• Treatment Outcome