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Cyclosporine A micellar delivery system for dry eyes

Authors Kang H, Cha K, Cho W, Park J, Park HJ, Sun BK, Hyun S, Hwang S

Received 1 March 2016

Accepted for publication 20 April 2016

Published 21 June 2016 Volume 2016:11 Pages 2921—2933


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

Han Kang,1,2 Kwang-Ho Cha,1 Wonkyung Cho,1 Junsung Park,1 Hee Jun Park,1 Bo Kyung Sun,1,2 Sang-Min Hyun,1,2 Sung-Joo Hwang1,2

1Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Incheon, South Korea

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.
Materials and 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.
Conclusion: The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes.

Keywords: cyclosporine A, Cremophor EL, micelle solution, dry eyes, Restasis

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