June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
In vitro Sustained Release of Tyrosine Kinase Inhibitors from Biodegradable PRINT Implants
Author Affiliations & Notes
  • Melissa Sandahl
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Kwadwo Caesar
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Janet Tully
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Mari Yang
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Stuart Williams
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Rhett M Schiffman
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Benjamin R Yerxa
    Envisia Therapeutics, Inc, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Melissa Sandahl, Envisia Therapeutics (E); Kwadwo Caesar, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (E); Mari Yang, Envisia Therapeutics (E); Stuart Williams, Envisia Therapeutics (E); Rhett Schiffman, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4458. doi:
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    • Get Citation

      Melissa Sandahl, Kwadwo Caesar, Janet Tully, Mari Yang, Stuart Williams, Rhett M Schiffman, Benjamin R Yerxa; In vitro Sustained Release of Tyrosine Kinase Inhibitors from Biodegradable PRINT Implants. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4458.

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

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Abstract

Purpose : Tyrosine kinase inhibitors (TKIs) are small molecules that have been found to inhibit angiogenesis through multiple targets. Recently TKIs have been under investigation to treat ocular conditions including macular degeneration. Drug delivery of TKI’s to the back of the eye is a challenge as (1) eye drop formulations do not allow for penetration into the target tissues and (2) IVT injections result in fast clearance of the small molecule API and clouding of the vitreous for crystalline suspensions. Here we demonstrate in vitro sustained release of TKIs using biodegradable implants designed for intravitreal delivery. TKIs can vary in chemical structure, potency, activity, melting point, and solubility; using PRINT, we can select tunable characteristics including implant size, shape, dose, release rate, and degradation rate to provide multiple month sustained release of several different TKIs.

Methods : Specific size and shape biodegradable PLGA/PLA implants were fabricated with controlled loadings of a TKI using proprietary PRINT technology. Implants were analyzed for morphology by scanning electron microscopy (SEM) and for TKI content by HPLC. In vitro release was monitored in 1X PBS, pH 7.4 with 1% Tween 80 at 37°C and analyzed by RP-HPLC.

Results : Biodegradable PLGA/PLA PRINT implants were fabricated with a high degree of mass uniformity and TKI content. SEM analysis showed uniform, controlled shape and size implants. Tunable and sustained release of several different TKIs was demonstrated in vitro lasting from two months up to six months or longer.

Conclusions : PRINT technology allows for the fabrication of fully biodegradable intraocular implants with uniform size, shape and dose. Here we show TKI compatibility with PRINT implants. We demonstrate the ability to tune the release of various TKI’s over several months in vitro.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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