April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Biodegradable Microparticle-Based Drug Delivery Systems for Modulating Ocular Surface Disease
Author Affiliations & Notes
  • E. Chang
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • W. J. Farley
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • D.-Q. Li
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • S. C. Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • C. S. De Paiva
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  E. Chang, None; W.J. Farley, None; D.-Q. Li, None; S.C. Pflugfelder, None; C.S. De Paiva, None.
  • Footnotes
    Support  NIH Grants EY11915 (SCP), Fight for Sight 2430063503 (EC), RPB, Oshman Foundation, William Stamps Farish Fund, Hamill Foundation and Allergan
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2416. doi:
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      E. Chang, W. J. Farley, D.-Q. Li, S. C. Pflugfelder, C. S. De Paiva; Biodegradable Microparticle-Based Drug Delivery Systems for Modulating Ocular Surface Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2416.

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

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Abstract

Purpose: : Continuous drug delivery to the ocular surface remains difficult due to the rapid tear clearance of topically applied agents. The purpose of this study was to evaluate biodegradable and biocompatible drug delivery systems on the ocular surface using poly-glycolic acid (PGA) or poly-lactic-co-glycolic acid (PLGA) based polymers.

Methods: : Fluorescent-labeled dextran or albumin and doxycycline were individually encapsulated into a PGA or PLGA-based matrix using a water-oil-water double emulsion method. The drug elution rates for various microspheres were evaluated spectrofluorometrically. Measurement of particle size was evaluated using image analysis. Subconjunctival injections of PGA/PLGA microspheres were used to evaluate safety and inflammatory response to the polymer on the murine ocular surface. The efficacy of the drug delivery system was evaluated by a single subconjunctival injection of PLGA-doxycycline (a broad metalloproteinase inhibitor) prior to induction of experimental dry eye (EDE) model in C57BL/6 mice for 5 days.

Results: : PGA and PLGA-based microspheres successfully elute encapsulated drugs of interest continuously over controlled periods of time. Mean PLGA-based microparticle diameter was 4.6 µm±1.54 µm. Yield synthesis was ~ 51% with > 99% of synthesized microparticles embedding the drug of interest. Drug elution rates and delivery time were easily modifiable by altering polymers and synthesis parameters. In vitro studies demonstrate successful continuous elution of encapsulated drugs for at least 2 weeks with an initial burst release phenomenon. Subconjunctival injections of fluorescent PGA/PGLA copolymers demonstrated dispersion of particles along the subconjunctival space and no inflammatory response. PLGA-doxycycline was efficacious in preventing EDE-induced corneal barrier disruption in experimental dry eye, similarly to topically applied doxycycline.

Conclusions: : PLGA/PGA-based drug delivery systems are safe and non-inflammatory. They can be successfully used to treat ocular diseases by continuously delivering biopharmaceuticals of interest.

Keywords: cornea: tears/tear film/dry eye • drug toxicity/drug effects • cornea: basic science 
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