April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Phenylboronic acid modified mucoadhesive nanoparticles facilitate weekly treatment of dry eye syndrome
Author Affiliations & Notes
  • Shengyan Liu
    Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
  • Chu Ning Chang
    Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
  • Mohit S Verma
    Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
  • Denise Hileeto
    Centre for Contact Lens Research - School of Optometry, University of Waterloo, Waterloo, ON, Canada
  • Alex Muntz
    Centre for Contact Lens Research - School of Optometry, University of Waterloo, Waterloo, ON, Canada
  • Ulrike Stahl
    Centre for Contact Lens Research - School of Optometry, University of Waterloo, Waterloo, ON, Canada
  • Jill Woods
    Centre for Contact Lens Research - School of Optometry, University of Waterloo, Waterloo, ON, Canada
  • Lyndon William Jones
    Centre for Contact Lens Research - School of Optometry, University of Waterloo, Waterloo, ON, Canada
  • Frank Gu
    Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
  • Footnotes
    Commercial Relationships Shengyan Liu, None; Chu Ning Chang, None; Mohit Verma, None; Denise Hileeto, None; Alex Muntz, None; Ulrike Stahl, None; Jill Woods, None; Lyndon Jones, None; Frank Gu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2160. doi:
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      Shengyan Liu, Chu Ning Chang, Mohit S Verma, Denise Hileeto, Alex Muntz, Ulrike Stahl, Jill Woods, Lyndon William Jones, Frank Gu; Phenylboronic acid modified mucoadhesive nanoparticles facilitate weekly treatment of dry eye syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2160.

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

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Abstract

Purpose: To develop mucoadhesive nanoparticle drug carriers that improve the precorneal retention of the drugs, and to evaluate their in vivo ocular irritancy response and efficacy in treating experimental dry eye by delivering Cyclosporine A (CycA).

Methods: The nanoparticles were formed using block copolymer poly(D,L-lactide)-b-dextran and surface functionalized with phenylboronic acid. The encapsulation and release properties of the nanoparticles were assessed using CycA. Experimental dry eye was induced in mice and treated with CycA loaded nanoparticles (weekly administration) and compared to RESTASIS®, administered three times daily. Assessments included tear volume, fluorescein staining, and histopathology. The nanoparticles, with or without CycA, were administered weekly to one eye of each rabbit, while the contralateral eye served as control. We examined the acute (1 week) and chronic (12 weeks) irritation responses using slit-lamp bio-microscope and histopathology.

Results: The nanoparticles encapsulated up to 11.2 wt% of CycA and sustained the release for 5 days. Histopathology demonstrated that administering CycA-loaded nanoparticles to dry eye-induced mice weekly eliminated inflammatory infiltrates and completely recovered the ocular surface. While thrice daily administration of RESTASIS® also cleared the inflammatory infiltrates, it showed much slower ocular surface recovery. Moreover, the weekly dosage of nanoparticles did not cause any irritation or inflammation throughout acute (1 week) and chronic (12 weeks) irritancy studies.

Conclusions: The mucoadhesive nanoparticle formulation significantly reduced administration frequency without compromising the therapeutic efficacy, while also improving the ocular surface recovery by eliminating irritation associated with frequent administration. The study provides promising results for the potential application of this formulation to dramatically improve therapeutic efficacy in treating anterior eye diseases.

Keywords: 608 nanomedicine • 489 cyclosporine • 620 ocular irritancy/toxicity testing  
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