September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Carbonic Anhydrase Inhibitor Encapsulation in Polyether-anhydride Microparticles for IOP Reduction
Author Affiliations & Notes
  • Jie Fu
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Ian F Pitha
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Fengying Sun
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Wenhua Liu
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Harry A Quigley
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Justin Hanes
    the Wilmer Eye institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Jie Fu, None; Ian Pitha, None; Fengying Sun, None; Wenhua Liu, None; Harry Quigley, None; Justin Hanes, None
  • Footnotes
    Support  NIH K12 EY15025-10
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5627. doi:
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    • Get Citation

      Jie Fu, Ian F Pitha, Fengying Sun, Wenhua Liu, Harry A Quigley, Justin Hanes; Carbonic Anhydrase Inhibitor Encapsulation in Polyether-anhydride Microparticles for IOP Reduction. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5627.

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

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Abstract

Purpose : Glaucoma is a leading cause of irreversible blindness worldwide. Topical ocular hypotensive medications are a mainstay of glaucoma treatment, however, they require patient adherence and can cause ocular surface toxicity. Controlled delivery of intraocular pressure (IOP) lowering medicine over several months could eliminate the need for daily drops and reduce ocular surface toxicity that often occurs with topical glaucoma medications. We have developed a microparticle formulation of dorzolamide intended for sustained IOP lowering after subconjunctival injection

Methods : Polyether-anhydride was synthesized by melt polycondensation. The carbonic anhydrase inhibitor (CAI) dorzolamide was encapsulated in biodegradable poly(ethylene glycol)-co-poly(sebacic acid)(PEG-PSA). Physiochemical characteristics of the particles were characterized in vitro prior to subconjunctival injection (5 mg dorzolamide) in normotensive, dutch belted rabbits (n=8). IOP was monitored in a blinded fashion and clinical exams of rabbits were followed until IOP normalization. Fluorescently labeled microparticles were injected subconjunctivally to tract particle retention in vivo (n=4).

Results : Drug loading was optimized by use of PEG-PSA polymer (14.9%). In vitro release of dorzolamide occurred in 12 days, however, subconjunctival injection reduced IOP up to 25% from baseline for over 30 days. Only mild, transient hyperemia was seen in particle-injected eyes on clinical exam. Fluorescently labeled particles were imaged in the subconjunctival space up to 52 days after injection.

Conclusions :
The results show promise in developing controlled release formulations of carbonic anhydrase inhibitors for subconjunctival delivery and sustained IOP reduction.

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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