April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Pharmacokinetic Measurements of a Sustained Drug Delivery System
Author Affiliations & Notes
  • R. A. Wassel
    Charlesson LLC, Oklahoma City, Oklahoma
  • D. Chen
    Charlesson LLC, Oklahoma City, Oklahoma
  • D. J. Nuno
    Charlesson LLC, Oklahoma City, Oklahoma
  • A. B. Quiambao
    Charlesson LLC, Oklahoma City, Oklahoma
  • J. L. Chodnicki
    Charlesson LLC, Oklahoma City, Oklahoma
  • Y. Hu
    Charlesson LLC, Oklahoma City, Oklahoma
  • P. Margaron
    Charlesson LLC, Oklahoma City, Oklahoma
  • J.-X. Ma
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  • R. Farjo
    Charlesson LLC, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  R.A. Wassel, None; D. Chen, None; D.J. Nuno, None; A.B. Quiambao, None; J.L. Chodnicki, None; Y. Hu, None; P. Margaron, None; J.-X. Ma, None; R. Farjo, None.
  • Footnotes
    Support  NIH/NEI EY017229, EY018301-01, Oklahoma Center for the Advancement of Science and Technology, Oklahoma Economic Development Generating Excellence Project 08-028
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5952. doi:
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    • Get Citation

      R. A. Wassel, D. Chen, D. J. Nuno, A. B. Quiambao, J. L. Chodnicki, Y. Hu, P. Margaron, J.-X. Ma, R. Farjo; Pharmacokinetic Measurements of a Sustained Drug Delivery System. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5952.

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

  • Supplements

Purpose: : The purpose of this study was to measure the drug concentration of CLT-003, a proprietary small molecule inhibitor of Hif1-, as it was released from polylactic-co-glycolic acid nanoparticles and microparticles in Dutch belted rabbits after intravitreal injection as well as in an in-vitro release model.

Methods: : Dutch Belted Rabbits were given an intravitreal injection of nanoparticles or microparticles containing CLT-003. Plasma was collected at multiple time points following administration and vitreous humor and retina were collected at 6 weeks post-injection. CLT-003 was extracted from the tissues with chloroform and measured via LC/MS. For the in-vitro model; various CLT-003 PLGA formulations were dialyzed against 60 ml of PBS (pH 7.4) at 37 ºC. Samples were collected at various time points and analyzed by HPLC.

Results: : The concentration of CLT-003 in plasma was minimal, as expected following local delivery. A therapeutic concentration of CLT-003 could be detected in the vitreous for 6 weeks, suggesting a depot for the drug in the vitreous. CLT-003 was also detected in the retina. Some of this drug was most likely from CLT-003 that was released from the nanoparticles/microparticles in the vitreous and diffused into the retina, as well as CLT-003 that was released from nanoparticles or microparticles intracellularly in the target retinal cells. The in-vitro model showed that for the majority of formulations (nanoparticles and microparticles) tested, at least 50% of the drug was still inside the nanoparticles after 60 days. Further time points are being collected and processed.

Conclusions: : CLT-003 PLGA-based formulations have demonstrated the ability to release the drug over a 6 week period. These results suggest these formulations may be developed into a suitable sustained release therapeutic that can be dosed intravitreally 1-3 times per year.

Keywords: diabetic retinopathy • retinal neovascularization • age-related macular degeneration 

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