December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
A New Method For Measuring Free Drug Concentration In Retinal Tissue
Author Affiliations & Notes
  • AO Koskelainen
    Lab of Biomedical Engineering Helsinki Univ of Technology Espoo Finland
  • S Nymark
    Lab of Biomedical Engineering Helsinki Univ of Technology Espoo Finland
  • C Haldin
    Dept of Biosciences
    Univ of Helsinki Helsinki Finland
  • H Tenhu
    Lab of Polymer Chemistry
    Univ of Helsinki Helsinki Finland
  • Footnotes
    Commercial Relationships   A.O. Koskelainen, None; S. Nymark, None; C. Haldin, None; H. Tenhu, None. Grant Identification: Support: TEKES Grant 40058/01
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3877. doi:
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      AO Koskelainen, S Nymark, C Haldin, H Tenhu; A New Method For Measuring Free Drug Concentration In Retinal Tissue . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3877.

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

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Abstract: : Purpose: We are studying the possibility to use thermoresponsive polymers to achieve rapid drug release from polymeric nanostructures induced by local tissue heating. As part of this work we developed a method for measuring the amount of drug released from polymeric nanostructures in neural tissue. The membrane permeable phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) was chosen as the model drug, because it reduces reversibly the amount of activable PDE, and thus slows down the photoresponse kinetics. When stimulus intensities are low enough, the photoresponses are linear (i.e. their kinetics do not depend on stimulus intensity), and their kinetics can be used as a measure of [IBMX]. Methods: Aspartate-isolated rod photoresponses to 519 nm flashes were recorded by electroretinogram (ERG) technique across isolated rat (Rattus norvegicus) retinas. The retinas were perfused with Ringer solution from the photoreceptor side. The photoresponse kinetics were determined as time-to-peak (tp) values of the small-stimulus (linear) photoresponses. The effect of IBMX was calibrated in the perfusate concentration range 3...300 µM. The polymeric nanostructures designed to bind hydrophobic drugs were loaded with IBMX and were then dissolved in Ringer. Results: The kinetics of linear photoresponses was a square root function of IBMX concentration in the range 3...300 µM: [IBMX]=a+btp2. The factors a and b were temperature-dependent and had to be determined separately for each retina and temperature. Our results suggest that the relative error of the method is less than 10% over the concentration range studied. Conclusion: 1) Our method enables accurate concentration determinations of the model drug IBMX in the retinal tissue in drug release experiments. 2) The [IBMX]-dependence of the photoresponse kinetics has to be "titrated" for each retina and temperature.

Keywords: 394 electrophysiology: non-clinical • 517 photoreceptors 

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