April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Effect Of Temperature, Light Intensity and Molecular Size On Photokinetic Transscleral Drug Delivery (PTD)
Author Affiliations & Notes
  • Tomasz A. Wiraszka
    Ophthalmology and Visual Sciences,
    University of Texas Medical Branch, Galveston, Texas
  • Gabriela A. Kulp
    Ophthalmology and Visual Sciences,
    University of Texas Medical Branch, Galveston, Texas
  • Edward R. Kraft
    Anesthesiology,
    University of Texas Medical Branch, Galveston, Texas
  • Aristides R. Koutrouvelis
    Anesthesiology,
    University of Texas Medical Branch, Galveston, Texas
  • Bernard F. Godley
    Ophthalmology and Visual Sciences,
    University of Texas Medical Branch, Galveston, Texas
  • Footnotes
    Commercial Relationships  Tomasz A. Wiraszka, None; Gabriela A. Kulp, Inventor-UTMB (P); Edward R. Kraft, Inventor-UTMB (P); Aristides R. Koutrouvelis, Inventor-UTMB (P); Bernard F. Godley, Inventor-UTMB (P)
  • Footnotes
    Support  Texas Ignition Fund, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3225. doi:https://doi.org/
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      Tomasz A. Wiraszka, Gabriela A. Kulp, Edward R. Kraft, Aristides R. Koutrouvelis, Bernard F. Godley; Effect Of Temperature, Light Intensity and Molecular Size On Photokinetic Transscleral Drug Delivery (PTD). Invest. Ophthalmol. Vis. Sci. 2011;52(14):3225. doi: https://doi.org/.

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

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Abstract

Purpose: : The effects of various physical factors on light-driven transscleral permeation of drugs were investigated to understand the mechanism of PTD, a novel non-invasive, drug delivery platform.

Methods: : Fresh ovine sclera was mounted in modified Franz cells for in vitro permeation studies. Model molecules were formulated in aqueous vehicles and pulsed with LEDs at target-specific wavelengths and pulse rates. To assess the impact of a fluorophore on a molecule's photokinetic mobility, fluorescein and rhodamine B were subjected to PTD and analyzed by fluorescence spectroscopy.To study the effect of temperature, PTD of human insulin was tested at 27, 36.5 and 42oC. Insulin levels were assayed by ELISA. The effect of light intensity on permeation of insulin was tested by varying LED output from 0.04 to 0.12 W/cm2. Morphological integrity of tissue subjected to PTD was assessed using hematoxylin and eosin staining.

Results: : Rhodamine B and fluorescein were detected in recipient fluid after PTD, but in quantities smaller than expected based on their size (only 1.5- 2 fold increase). Six compounds with molecular weights ranging from 454 Da to 4500kDa were subjected to PTD and treatment resulted in 2-59 fold increase in permeation vs control. At all temperatures tested, PTD permeation was significantly higher than passive (p<0.001), however there was no difference among active cells.We found no difference in the final amount of insulin in the recipient cells when LED output was increased 2-3 fold (p=0.962). However, all of the PTD permeation levels were significantly higher than passives (p<0.05). Light microscopy of the tissue sections did not show significant morphologic differences between samples from PTD and passive groups.

Conclusions: : PTD is a novel, noninvasive transscleral delivery platform useful for a broad range of molecular sizes. The mechanism, while not fully understood, appears to be independent of light intensity or temperature, and does not produce adverse morphologic effects in sclera tissue. Presence of a fluorophor moiety on the molecule seems to have a negative impact on permeation.

Keywords: sclera • drug toxicity/drug effects 
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