June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
In Vivo Sustained Release of Rapamycin (Sirolimus) from a Biodegradable Intravitreal Device
Author Affiliations & Notes
  • Mynna Ishikiriyama
    Ophthalmology, Santa Casa of Sao Paulo, Niteroi, Brazil
    Ophthalmology, UCSF, San Francisco, CA
  • Kevin Lance
    Ophthalmology, UCSF, San Francisco, CA
  • Sam Good
    Ophthalmology, UCSF, San Francisco, CA
  • Thais Sousa Mendes
    Ophthalmology, Santa Casa of Sao Paulo, Niteroi, Brazil
    Ophthalmology, UCSF, San Francisco, CA
  • kazuhito yamada
    Santen, Osaka, Japan
  • hiroyuki asada
    Santen, Osaka, Japan
  • Tejal Desai
    Ophthalmology, UCSF, San Francisco, CA
  • Robert B Bhisitkul
    Ophthalmology, UCSF, San Francisco, CA
  • Footnotes
    Commercial Relationships Mynna Ishikiriyama, None; Kevin Lance, None; Sam Good, None; Thais Mendes, None; kazuhito yamada, Santen INC. (E); hiroyuki asada, Santen (E); Tejal Desai, None; Robert Bhisitkul, Aerpio (C), Allergan (C), Bausch Lomb (C), Genentech (C), Genentech (F), GlaxoSmithKline (F), Iconic (C), Santen Inc. (C), Xoma (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 231. doi:
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    • Get Citation

      Mynna Ishikiriyama, Kevin Lance, Sam Good, Thais Sousa Mendes, kazuhito yamada, hiroyuki asada, Tejal Desai, Robert B Bhisitkul; In Vivo Sustained Release of Rapamycin (Sirolimus) from a Biodegradable Intravitreal Device. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):231.

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

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Abstract

Purpose: The goal of this study is to show the in vivo pharmacokinetics of a sustained drug delivery device containing rapamycin, which is currently used as an immunosuppressant drug for the treatment of uveitis.

Methods: Polycaprolactone (PCL) thin film devices were implanted in 11 New Zealand White rabbit eyes. Two device types were used, a microporous device and a rapamycin-loaded film device. The microporous device is two microporous PCL films around a rapamycin pellet. The rapamycin-loaded film device is composed of PCL films with rapamycin incorporated throughout the film surrounding a rapamycin pellet.<br /> <br /> We separated the rabbits in 3 groups. An "acute" group (6 rabbits) in which we implanted the microporous device and collected samples only at sacrifice on weeks 4,8,16. An "Intrector" group (3 rabbits) which received the microporous device as well, but with vitreous collected at 1,2,4,8,12 weeks via vitrectomy and total vitreous taken at 16 weeks at sacrifice. A "special" group (2 rabbits) in which we implanted rapamycin-loaded film devices and collected the samples at the same timepoints as the Intrector group.

Results: For the “acute” group of devices rapamycin was in the vitreous at a stable level from week 4 until week 16, between 1.3 and 5.3 ng/mL. Concentrations of rapamycin in the retina-choroid remained stable from week 4 until week 16, between 107 and 255 ng/g with one outlier at 1,070 ng/g. At 16 week sacrifice, “Intrector” group rabbits had vitreous rapamycin concentrations between 2.6 and 11.1 ng/mL and retina-choroid concentrations between 134 and 318 ng/g. At 16 week sacrifice, “special” group rabbits had vitreous rapamycin concentrations between 3.1 and 18.1 ng/mL and retina-choroid concentrations between 53.2 and 115 ng/g.<br /> <br /> Microvitrectomy samples taken from the “Intrector” group averaged 1.2 ng/mL (std. dev. 0.85) and the “special” groups averaged 0.55 ng/mL (std. dev. 0.27), lower than the values for whole vitreal samples by a factor of 3.6 and 18, respectively

Conclusions: The devices released rapamycin at a stable rate for up to 16 weeks. Rapamycin was detected at a consistent concentration in the vitreous and the retina-choroid. Adding rapamycin into the film of the device did not significantly alter the release behavior. Microvitrectomy sampling was not representative of the total vitreal concentration for rapamycin as determined by sampling of the complete vitreous.

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