April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
In vivo Evaluation of Ocular Residence Time of 124I-labelled Thiolated Chitosan in Rabbits Using MicroPET Technology
Author Affiliations & Notes
  • D. Dangl
    Research, Croma-Pharma GmbH, Leobendorf, Austria
  • M. Hornof
    Research, Croma-Pharma GmbH, Leobendorf, Austria
  • M. Hoffer
    Research, Croma-Pharma GmbH, Leobendorf, Austria
  • C. Kuntner
    Radiopharmaceuticals & MicroPET Imaging, Austrian Research Centers GmbH - ARC, Seibersdorf, Austria
  • T. Wanek
    Radiopharmaceuticals & MicroPET Imaging, Austrian Research Centers GmbH - ARC, Seibersdorf, Austria
  • H. Kvaternik
    Radiopharmaceuticals & MicroPET Imaging, Austrian Research Centers GmbH - ARC, Seibersdorf, Austria
  • Footnotes
    Commercial Relationships  D. Dangl, Croma-Pharma, E; M. Hornof, Croma-Pharma, E; M. Hoffer, Croma-Pharma, E; C. Kuntner, Croma-Pharma, F; T. Wanek, Croma-Pharma, F; H. Kvaternik, Croma-Pharma, F.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3689. doi:
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      D. Dangl, M. Hornof, M. Hoffer, C. Kuntner, T. Wanek, H. Kvaternik; In vivo Evaluation of Ocular Residence Time of 124I-labelled Thiolated Chitosan in Rabbits Using MicroPET Technology. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3689.

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

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Abstract

Purpose: : The ocular residence time and biodistribution of a topically applied thiolated polymer - chitosan-N-acetylcysteine conjugate (chitosan-NAC) - was evaluated in rabbits using microPET technology. It is postulated that interaction between thiol groups of the chitosan-NAC with cysteine-rich mucin (MUC5AC) increases residence time of the polymer on the ocular surface and tear film stability.

Methods: : Two different eye drop formulations of chitosan-NAC (0.3% and 0.5%) spiked with covalently 124I-labelled chitosan-NAC were evaluated. An aqueous solution of Na124I and a formulation containing unmodified chitosan (0.5%) spiked with 124I-labelled chitosan served as controls. Four rabbits were used per group and each rabbit received one drop (35 µl) of the test formulation in one eye. Distribution of the radioactive marker in the head region was measured at 5 different time points between 0 and 22 hours after topical eye drop application. Regions of interest were manually defined in the reconstructed PET images. Tracer uptake was quantified as percent applied dose per gram tissue.

Results: : After application of 0.3% and 0.5% chitosan-NAC formulations radioactivity was detected on the ocular surface during the entire imaging period (up to 22 hours). Ocular surface distribution of the 124I-labelled 0.3% chitosan-NAC formulation was homogeneous, whereas after application of the 0.5% chitosan-NAC formulation the highest activity levels were detected in the inner canthus. The aqueous solution of Na124I was only detected during the first hour after application.

Conclusions: : The study showed that ocular residence time and biodistribution of 124I-labelled polymers can be measured using microPET technology. Whereas an aqueous solution of Na124I was rapidly cleared from the eye, 124I-labelled chitosan-NAC remained located on the ocular surface during the entire observation period of 22 hours.

Keywords: cornea: tears/tear film/dry eye • cornea: surface mucins • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) 
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