September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Development of a semi-permanent, controlled release antibiotic eye drop
Author Affiliations & Notes
  • Morgan V Fedorchak
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Regis P Kowalski
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Eric G Romanowski
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Joel S Schuman
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Steven R Little
    Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Morgan Fedorchak, None; Regis Kowalski, None; Eric Romanowski, None; Joel Schuman, None; Steven Little, None
  • Footnotes
    Support  NIH 1R01EY024039, Unrestricted Grant from Resarch to Prevent Blindness, Commonwealth of Pennsylvania, P30 EY008098, Eye and Ear Foundation of Pittsburgh
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 764. doi:
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    • Get Citation

      Morgan V Fedorchak, Regis P Kowalski, Eric G Romanowski, Joel S Schuman, Steven R Little; Development of a semi-permanent, controlled release antibiotic eye drop. Invest. Ophthalmol. Vis. Sci. 2016;57(12):764.

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

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Abstract

Purpose : The purpose of this study was to adapt a controlled release formulation that has been previously validated for glaucoma treatment to release moxifloxacin in a rabbit endophthalmitis model. This novel system combines a thermoresponsive hydrogel with drug-loaded, degradable polymer microspheres to autonomously deliver the full course of drug to achieve infection prophylaxis. The gel/microsphere delivery system is administered topically, similarly to a traditional eye drop, and eliminates the need for frequent drop administration or more invasive implants to maintain therapeutic drug levels.

Methods : Moxifloxacin-loaded microspheres (MMS) were prepared using a standard double emulsion technique with poly(lactic-co-glycolic acid) in the oil phase. We fabricated two distinct MMS formulations by varying NaCl concentration in the inner aqueous phase, with the goal of achieving both a one-day "burst" release and a more sustained week-long release profile. The resulting MMS were tested in vitro for average diameter, surface morphology, drug release, and overall loading. MMS were then suspended in gel and the gel properties including transition temperature, time, swelling ratio, and degradation, were measured. For in vivo studies, a single 100ul drop of gel containing approximately 10mg of MMS was administered just prior to inoculation with S. aureus. Positive control animals received 5 drops of Vigamox prior to inoculation followed by one immediately post inoculation and 4 over the following 24 hours. Negative control animals received a single gel drop containing blank microspheres. Animals were scored for endophthalmitis just prior to sacrifice after 24 hours, with subsequent microbiological assessment.

Results : In vitro drug release assays showed a 24h burst release and a 7d sustained release for the 1d and 1w formulations, respectively. The single gel/microsphere drop controlled for endophthalmitis in 100% of animals, comparable to the positive control group, while the negative control group resulted in 100% positive endophthalmitis scores. These results were confirmed by microbiological assessment, with 0% of animals in the test and positive control groups showing bacterial growth upon culture.

Conclusions : In this study we have demonstrated the ability of a single, gel-based drop to achieve endophthalmitis prophylaxis comparable to frequent adminsitration of standard moxifloxacin drops.

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

 

Gel/microsphere suspension

Gel/microsphere suspension

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