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 journalArticle

14 Citations (Scopus)

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. 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
Volume11
DOIs
Publication statusPublished - 2016 Jun 21

Fingerprint

Micelles
Cyclosporine
Goblet Cells
Tears
Particle Size
Rabbits
Conjunctiva
Particle size
Osmolar Concentration
Dry Eye Syndromes
Drug Compounding
Ophthalmic Solutions
Chemical stability
Hematoxylin
Eosine Yellowish-(YS)
Buffers
Phosphates
Ethanol
Epithelium
Cell Count

All Science Journal Classification (ASJC) codes

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

Cite this

Kang, Han ; Cha, Kang Ho ; Cho, Wonkyung ; Park, Junsung ; Park, Hee Jun ; Sun, Bo Kyung ; Hyun, Sang Min ; Hwang, Sung Joo. / Cyclosporine A micellar delivery system for dry eyes. In: International journal of nanomedicine. 2016 ; Vol. 11. pp. 2921-2933.
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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. 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.",
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Kang, H, Cha, KH, Cho, W, Park, J, Park, HJ, Sun, BK, Hyun, SM & Hwang, SJ 2016, 'Cyclosporine A micellar delivery system for dry eyes', International journal of nanomedicine, vol. 11, pp. 2921-2933. https://doi.org/10.2147/IJN.S107569

Cyclosporine A micellar delivery system for dry eyes. / Kang, Han; Cha, Kang Ho; Cho, Wonkyung; Park, Junsung; Park, Hee Jun; Sun, Bo Kyung; Hyun, Sang Min; Hwang, Sung Joo.

In: International journal of nanomedicine, Vol. 11, 21.06.2016, p. 2921-2933.

Research output: Contribution to journalArticle

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Kang H, Cha KH, Cho W, Park J, Park HJ, Sun BK et al. Cyclosporine A micellar delivery system for dry eyes. International journal of nanomedicine. 2016 Jun 21;11:2921-2933. https://doi.org/10.2147/IJN.S107569