Cyclosporine A micellar delivery system for dry eyes

Han Kang, Kang Ho Cha, Wonkyung Cho, Junsung Park, Hee Jun Park, Bo Kyung Sun, Sang Min Hyun, Sung Joo Hwang

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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. 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.

Original languageEnglish
Pages (from-to)2921-2933
Number of pages13
JournalInternational journal of nanomedicine
Publication statusPublished - 2016 Jun 21

Bibliographical note

Funding Information:
This work was supported by the Mid-career Researcher Program through a National Research Foundation grant funded by the Ministry of Science, ICT, and Future Planning, South Korea (NRF-2014R1A2A2A01005059).The authors were also assisted by Byung Joon Park, who helped with the English revisions and contributed ideas to the “Results and discussion” section.

Publisher Copyright:
© 2016 Kang et al.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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