April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Precisely Engineered Biodegradable Drug Delivery Systems for the Extended Release of Prostaglandin Analogues in the Anterior Chamber
Author Affiliations & Notes
  • Andres Garcia
    Envisia Therapeutics, Research Triangle Park, NC
  • Janet Tully
    Envisia Therapeutics, Research Triangle Park, NC
  • Sanjib Das
    Envisia Therapeutics, Research Triangle Park, NC
  • Tyler Pegoraro
    Envisia Therapeutics, Research Triangle Park, NC
  • Leo Trevino
    Envisia Therapeutics, Research Triangle Park, NC
  • Benjamin Maynor
    Envisia Therapeutics, Research Triangle Park, NC
  • Tomas Navratil
    Envisia Therapeutics, Research Triangle Park, NC
  • Benjamin R Yerxa
    Envisia Therapeutics, Research Triangle Park, NC
  • Footnotes
    Commercial Relationships Andres Garcia, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (E); Sanjib Das, Envisia Therapeutics (E); Tyler Pegoraro, Envisia Therapeutics (E); Leo Trevino, Envisia Therapeutics (E); Benjamin Maynor, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5268. doi:https://doi.org/
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      Andres Garcia, Janet Tully, Sanjib Das, Tyler Pegoraro, Leo Trevino, Benjamin Maynor, Tomas Navratil, Benjamin R Yerxa; Precisely Engineered Biodegradable Drug Delivery Systems for the Extended Release of Prostaglandin Analogues in the Anterior Chamber. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5268. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

Biodegradable intraocular implants are one of the most attractive alternatives to achieve extended release of actives in the eye, bypassing issues associated with patient non-compliance and significantly improving therapeutic and safety profiles. However, the ability to precisely fabricate intracameral implants for the extended release of prostaglandin analogues (PGAs) in the anterior chamber with reproducible size, shape and dose has proven elusive with current technologies (i.e. hot-melt extrusion, in-situ gelation). The ability to reproducibly fabricate implants in the 100 μm to 3,000 μm size range enables for simple insertion and anatomically compatible placement of PGA drug delivery systems at the iridocorneal angle for the sustained reduction of elevated intraocular pressure in patients with glaucoma.

 
Methods
 

We report the ability to precisely fabricate intraocular implants comprised of a blend of PGA, polylactic acid (PLA) and/or poly(lactic-co-glycolic) acid (PLGA) for the tunable release of actives using the PRINT® (Particle Replication in Non-wetting Templates) technology. PGA dose content uniformity and in-vitro release of PGA from the implants in physiologically relevant media at 37°C over time were evaluated.

 
Results
 

Envisia’s PRINT micromolding technology uses templates (Figure 1A) to fabricate PGA/PLA/PLGA implants with precise and anatomically relevant size and shape (Figure 1B, Figure 1C and Figure 1D). Implants with low PGA doses and high degree of dose content uniformity (10.6 μg, ±0.5 μg) were achieved. Moreover, the technology offers the ability to formulate implants with tunable release profiles over therapeutically relevant timelines in-vitro, from a few weeks to several months (Figure 1E).

 
Conclusions
 

The PRINT technology uniquely allows for the fabrication of intracameral implants with uniform size, shape and dose. We demonstrated the ability to fabricate PGA/PLA/PLGA intracameral implants in the desirable size range of 100 μm to 3,000 μm for extended release of PGA where anatomical constraints may call for uniquely engineered implants.

 
 
Figure 1: PRINT Technology: A) mold template, B) implants on array, C) implant in needle, D) size comparison between two PRINT implants and a dime, E) in-vitro release of PGA from PRINT implants with durations of action from weeks to several months.
 
Figure 1: PRINT Technology: A) mold template, B) implants on array, C) implant in needle, D) size comparison between two PRINT implants and a dime, E) in-vitro release of PGA from PRINT implants with durations of action from weeks to several months.
 
Keywords: 568 intraocular pressure • 420 anterior chamber  
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