May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Long Term Protein Stability in a Biodegradable Polysaccharide Drug Delivery Implant
Author Affiliations & Notes
  • M. Burkstrand
    Protein Delivery, SurModics, Eden Prairie, Minnesota
  • B. Jelle
    Protein Delivery, SurModics, Eden Prairie, Minnesota
  • J. Wall
    Protein Delivery, SurModics, Eden Prairie, Minnesota
  • J. Zhou
    Ophthalmology, SurModics, Irvine, California
  • S. Erickson
    Ophthalmology, SurModics, Irvine, California
  • Footnotes
    Commercial Relationships  M. Burkstrand, SurModics,Inc., E; B. Jelle, SurModics, Inc., E; J. Wall, SurModics, Inc., E; J. Zhou, SurModics, Inc., E; S. Erickson, SurModics, Inc., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3183. doi:https://doi.org/
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    • Get Citation

      M. Burkstrand, B. Jelle, J. Wall, J. Zhou, S. Erickson; Long Term Protein Stability in a Biodegradable Polysaccharide Drug Delivery Implant. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3183. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

Demonstrate stabilization of bioactive protein in a degradable polysaccharide matrix system designed for sustained, controlled release of therapeutic agents into the vitreous.

 
Methods:
 

Rod-shaped devices 5 mm in length and 0.5 mm in diameter were formed using modified, low molecular weight polysaccharides (PS) and incorporating 100 µg of a 49 kD rabbit-anti-goat antibody fragment [f(ab)] as a model protein. Devices containing f(ab) [PS Formulation 1 or Formulation 2] were implanted in the vitreous of Dutch-belted rabbit eyes. At 3, 7, 14, 28, 84, and 168 days, the devices were explanted and assayed for remaining functional and total f(ab) using ELISA. Functionality in this study was defined as the ability of the f(ab) to bind to a goat antigen. Vitreous samples at these timepoints were similarly assayed via ELISA for functional f(ab).

 
Results:
 

Of the 30 implanted animals, all remained in good general health throughout the study. Follow-up examinations reflected good biocompatibility and tolerance. Following enucleation, the devices, either fully intact or in smaller, multiple pieces, were removed from the eyes. Explanted devices (n=5/timepoint for each formulation) were analyzed for mean functional and total f(ab) detected and revealed that on average ≥ 80 % of the f(ab) retained functionality after extended times in vivo (Table 1). Functional f(ab) assayed in the vitreous also demonstrated sustained protein release from these devices over a number of weeks that correlated with the corresponding mass loss of the devices.Table 1: Detection by ELISA of total and functional f(ab) in explanted devices and the vitreous of rabbits at predefined timepoints  

 
Conclusions:
 

The polysaccharide devices were demonstrated to be well tolerated in this study. It is possible to form devices from modified, low molecular weight polysaccharides that have sufficient density to stabilize and protect retained proteins when implanted intravitreally. The detected f(ab) in the explanted devices remained stable at each timepoint, as demonstrated by the high % functionality of recovered protein.

 
Keywords: protein structure/function 
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