April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Ocular Safety Evaluation of Newly Developed Cyclosporine in Cationic Emulsion in an in vitro Corneal Wound Healing Model and in an Acute in vivo Rabbit Model
Author Affiliations & Notes
  • Hong Liang
    Ophthalmology-Hosp Paris, Chino Des Quinze-Vights, Paris, France
    INSERM, UMR_S968, UPMC University, Vision Institute, Paris, France
  • Christophe Baudouin
    Ophthalmology-Hosp Paris, Chino Des Quinze-Vights, Paris, France
    INSERM, UMR_S968, UPMC University, Vision Institute, Paris, France
  • Phillipe Daull
    Novagali Pharma, Evry, France
  • Luisa Riancho
    INSERM, UMR_S968, UPMC University, Vision Institute, Paris, France
  • Jean-Sébastien Garrigue
    Novagali Pharma, Evry, France
  • Françoise Brignole-Baudouin
    INSERM, UMR_S968, UPMC University, Vision Institute, Paris, France
    Paris Descartes University, Faculty of Pharmaceutical and Biological Sciences, Toxicology Department, Paris, France
  • Footnotes
    Commercial Relationships  Hong Liang, The study was supported by an unrestricted grant from Novagali Pharma and Quinze-Vingts Hospital. (I); Christophe Baudouin, Consultant for Novagali Pharma (I); Phillipe Daull, Novagali Pharma Employee (E); Luisa Riancho, None; Jean-Sébastien Garrigue, Employee of Novagali Pharma (E); Françoise Brignole-Baudouin, None
  • Footnotes
    Support  unrestricted grant from INSERM
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2026. doi:
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      Hong Liang, Christophe Baudouin, Phillipe Daull, Luisa Riancho, Jean-Sébastien Garrigue, Françoise Brignole-Baudouin; Ocular Safety Evaluation of Newly Developed Cyclosporine in Cationic Emulsion in an in vitro Corneal Wound Healing Model and in an Acute in vivo Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2026.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Topical preparation of cyclosporine (CsA) has been developed to treat dry eye while inducing side effects, such as allergy and irritation. The present study aims at evaluating the cytotoxicity profile of newly developed CsA in cationic emulsion (CEm) (a) in an in vitro corneal would healing model using human corneal epithelial (HCE) cells (b) and in an acute in vivo rabbit model.

Methods: : Four CsA formulations were tested: 1) 0.05%CsA-0.005% cetalkonium chloride (CKC)-CEm, 2) 0.05%CsA-0.02% benzalkonium chloride (BAC)-CE, 3) 0.05%CsA-oil solvent excipient (Oi), commercial 0.05%CsA-Em (Restasis®). Phosphate buffered saline (PBS) was used as control. (a) A wound was created by scratching through a confluent HCE cell layer. Cytotoxicity, cell migration and proliferation were analyzed at 2, 24 and 72hours after a 30 min exposure to solutions diluted to 1/10; (b) The eye drops were applied to rabbit eyes 15 times at 5-min intervals, and the ocular surface structures were examined using slit-lamp and corneal in vivo confocal microscopy (IVCM).

Results: : (a) The in vitro study showed that CsA-BAC delayed corneal healing process by damaging dramatically the remaining HCE cells. The other solutions maintained a normal healing rate with a particular behavior for CsA-CKC that improves the healing process when compared to control. (b) CsA associated to BAC showed the highest toxicity by clinical observations and IVCM, inducing redness, chemosis with damaged corneal epithelium and inflammatory infiltration. CsA-Oi and CsA-Em induced moderate inflammatory cell infiltration around the conjunctiva-associated lymphoid tissue structures, and CsA-CKC showed the lowest toxicity with patterns similar to those of the control.

Conclusions: : The combination of these in vitro and in vivo models evaluated the tolerance/cytotoxicity and the dynamic wound healing potential of CsA in different formulations. The CsA in cationic emulsion appeared to offer the best tolerance without delaying HCE healing. It will be of great interest to protect dry eye surface and improve long-term tolerance of CsA topical treatments.

Keywords: cyclosporine • wound healing • drug toxicity/drug effects 
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