June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The Monthly Eye Drop: Development of a Long-term, Noninvasive Glaucoma Treatment System
Author Affiliations & Notes
  • Morgan Fedorchak
    University of Pittsburgh, Pittsburgh, PA
    McGowan Institute for Regenerative Medicine, Pittsburgh, PA
  • Anthony Cugini
    University of Pittsburgh, Pittsburgh, PA
  • Joel Schuman
    University of Pittsburgh, Pittsburgh, PA
    UPMC Eye Center, Pittsburgh, PA
  • Steven Little
    University of Pittsburgh, Pittsburgh, PA
    McGowan Institute for Regenerative Medicine, Pittsburgh, PA
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4294. doi:
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    • Get Citation

      Morgan Fedorchak, Anthony Cugini, Joel Schuman, Steven Little; The Monthly Eye Drop: Development of a Long-term, Noninvasive Glaucoma Treatment System. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4294.

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

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Abstract
 
Purpose
 

IOP reduction in patients with glaucoma is typically accomplished through the administration of medicated eye drops several times daily, the difficult and frequent nature of which contributes to low patient compliance rates. Newer drug delivery methods for glaucoma require clinician administration of invasive injections or implants. The purpose of this study was to develop and test a hydrogel/microparticle formulation that provides one month of brimonidine tartrate (BT) from a noninvasive, patient-administered drop.

 
Methods
 

BT-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles and poly-(N-isopropylacrylamide)/poly(ethylene glycol) (pNIPAAm/PEG) hydrogels were combined following polymerization of the gel. The gel/microparticle formulation was characterized for degradation and BT release for over one month. Additionally, a single drop was administered to the inferior fornix of New Zealand white rabbits. IOP was measured periodically using tonometry and histology was used to assess biocompatibility of the gel/microparticle system.

 
Results
 

Microparticles were confirmed to have a diameter of 7.5±2.9 μm with a primarily poreless morphology. The pNIPAAm gel demonstrated a lower critical solution temperature (LCST) of approximately 34°C. Degradation of the gel was negligible. Drug release was within the calculated therapeutic range of topical BT drops (Figure 2). Cytotoxicity testing demonstrated no significant effect on conjunctival cell viability. In vivo testing demonstrated that the gel/microparticle drop could be easily administered and form a stable, opaque gel (Figure 1). The gel eye drop was easily removed, leaving no evidence of gel or microparticles.

 
Conclusions
 

This controlled-release BT delivery system represents a simple and novel patient-administered formulation that we believe will provide adequate IOP reduction and biocompatibility without the need for intraocular injections or frequent drop administration.

 
 
Figure 1: In vivo testing of thermo-gelling eye drop demonstrating A) administration of liquid drop, B) rapid gelling in the lower fornix, and C) simple removal with tweezers.
 
Figure 1: In vivo testing of thermo-gelling eye drop demonstrating A) administration of liquid drop, B) rapid gelling in the lower fornix, and C) simple removal with tweezers.
 
 
Figure 2: In vitro release of brimonidine tartrate from PLGA microparticles alone and combined with pNIPAAm gels (n=3). Also shown are the theoretical maximum and minimum amounts of BT absorbed from traditional eye drops, based on 2 drops per day of 0.15% BT solution and 1-7% absorption.
 
Figure 2: In vitro release of brimonidine tartrate from PLGA microparticles alone and combined with pNIPAAm gels (n=3). Also shown are the theoretical maximum and minimum amounts of BT absorbed from traditional eye drops, based on 2 drops per day of 0.15% BT solution and 1-7% absorption.
 
Keywords: 568 intraocular pressure • 503 drug toxicity/drug effects • 561 injection  
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