May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Hydrophobic Biodegradable Polysaccharide Implant for Controlled Drug Delivery
Author Affiliations & Notes
  • J. Missling
    SurModics, Eden Prairie, Minnesota
  • P. Barnett
    SurModics, Eden Prairie, Minnesota
  • S. Erickson
    SurModics, Irvine, California
  • Footnotes
    Commercial Relationships  J. Missling, SurModics, E; P. Barnett, SurModics, E; S. Erickson, SurModics, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5004. doi:https://doi.org/
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    • Get Citation

      J. Missling, P. Barnett, S. Erickson; Hydrophobic Biodegradable Polysaccharide Implant for Controlled Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5004. doi: https://doi.org/.

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

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Abstract

Purpose: : First, to compare and contrast in-vitro and in-vivo drug elution profiles for a hydrophobic biodegradable polysaccharide ocular implant. Second, to confirm the devices are capable of delivering pharmaceutically active agents to ocular tissue in a sustained and controllable manner. Third, to assess the safety of the device in an animal model.

Methods: : Biodegradable devices comprised of a hydrophobically modified polysaccharide and triamcinolone acetonide (TA), 50% w/w; were fabricated by a solventless extrusion process. Materials were fed in dry powder or pellet form to an extruder which uniformly mixed the components at a temperature sufficient to melt the polymeric materials but not the TA. The resulting mixture was extruded through a cylindrical die to form a 500 micrometer diameter rod. The cooled extrudate was cut to 5 millimeter lengths to form devices with a total mass of approximately 1 mg. Two distinct formulations were developed, each containing approximately 500 ug of TA.In-vitro elution of TA was determined by repeated exchanges of 4 mL phosphate buffered saline, pH 7.4, agitated and maintained at 37oC, at appropriate time intervals. The concentration of TA in the extraction media at each time point was quantified by UV-vis spectroscopy.In-vivo elution profiles were determined by implanting sterilized devices into the vitreous of Dutch Belted Rabbits, using a minimally invasive surgical technique, and explanting the devices at different time points. The explants were then assayed for drug content via HPLC to determine how much drug had been released.Optical microscopy was performed to characterize changes in geometric features and surface appearance of the devices.

Results: : The two implant formulations (Slow and Fast Doses) released TA in-vitro at an average rate of 0.2 µg/day and 2.5 µg/day, respectively, over days 20 - 40, with cumulative average release of 13 µg TA and 186 µg TA, respectively, at 28 days. In-vivo average cumulative TA release trended slightly faster, with 25 µg released from the Slow Dose at 28 days and 220 µg released from the Fast Dose at 28 days. The mechanical integrity of the device was sufficient to survive the implant procedure.

Conclusions: : A biodegradable implant has been developed that provides sustained and controlled release of TA to ocular tissue in an animal model. Extrapolation of elution data predicts TA release from the Fast Dose will extend to 60 days, while the Slow Dose is anticipated to last greater than 30 months. The device was fabricated into a shape and size suitable for minimally invasive implantation into the vitreous space.

Keywords: vitreous • corticosteroids • injection 
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