September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Mucoadhesive nanoparticle eye drop platform: tracking of ocular retention and treatment of experimental dry eye
Author Affiliations & Notes
  • Shengyan Liu
    Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada
  • Matthew Dozois
    Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada
  • Chu Ning Chang
    Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada
  • Denise Hileeto
    Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada
  • Huiyuan Liang
    Keenan Research Centre for BIomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Department of Opthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Matthew-Mina Reyad
    Keenan Research Centre for BIomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Department of Opthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Shelley R Boyd
    Keenan Research Centre for BIomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Department of Opthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Lyndon William Jones
    Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada
  • Frank Gu
    Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada
  • Footnotes
    Commercial Relationships   Shengyan Liu, WO2013188979 A1 (P); Matthew Dozois, None; Chu Ning Chang, None; Denise Hileeto, None; Huiyuan Liang, None; Matthew-Mina Reyad, None; Shelley Boyd, None; Lyndon Jones, WO2013188979 A1 (P); Frank Gu, WO2013188979 A1 (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3990. doi:
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    • Get Citation

      Shengyan Liu, Matthew Dozois, Chu Ning Chang, Denise Hileeto, Huiyuan Liang, Matthew-Mina Reyad, Shelley R Boyd, Lyndon William Jones, Frank Gu; Mucoadhesive nanoparticle eye drop platform: tracking of ocular retention and treatment of experimental dry eye. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3990.

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

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Abstract

Purpose : Patients suffering from dry eye (DE) syndrome struggle with the requirement to instill multiple daily applications of eye drops, resulting in poor compliance and subsequent reduced efficacy. We hypothesize that we can significantly reduce eye drop dosage for the treatment of DE by using mucoadhesive nanoparticles (MNPs) as drug carriers.

Methods : Ocular surface retention was studied by measuring the amount of fluorescence after delivering MNPs encapsulating fluorescent dye Indocyanine Green (ICG) as a model drug to the eyes of NZW male rabbits. Experimental DES in mice (C57BL/6; female) was induced by applying scopolamine patches to their midtails and exposing them to desiccating environments. These mice were treated with various formulations including Restasis® (thrice daily), MNPs without Cyclosporine A (CsA) (once a week), CsA-loaded MNPs (MNP-CsA 0.005-0.01%; once a week) or MNP-CsA 0.025% (once a week) for a month. Dry eye status was evaluated using tear production measurement, corneal fluorescein clearance, and histopathology analysis.

Results : The MNPs enhanced the retention of the ICG on the ocular surface for up to 24 hrs compared to free ICG. After a month long treatment, MNP-CsA 0.005-0.01% (once a week) demonstrated elimination of obvious inflammation and total ocular surface recovery, whereas the administration of Restasis® (thrice daily) or MNP-CsA 0.025% (once a week) only achieved elimination of inflammatory signs, without complete recovery of the ocular surface tissues evident by inadequate number of surface goblet cells. The MNPs demonstrated significant reduction in dosage of the formulation for effective treatment of experimental DE, by prolonging the ocular retention of the active pharmaceutical ingredients.

Conclusions : The results are consistent with our hypothesis that the MNPs can significantly improve ocular surface retention of the drugs and, therefore, significantly decrease both the administration frequency and the dosage of the formulation for treatment of experimental DE. The MNP eye drop platform demonstrated prolonged ocular surface retention of ICG in rabbits and effective treatment of dry eye conditions in mice, with up to 50 to 100 fold reduction in overall dosage of CsA compared to Restasis®, which will improve patient compliance and may significantly reduce side effects.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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