April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Non-invasive Delivery Of Human Insulin Into The Posterior Segment Of The Rabbit Eye Using Photokinetic Transscleral Drug Delivery
Author Affiliations & Notes
  • Bernard F. Godley
    Ophthal & Visual Sciences,
    Univ of Texas Medical Branch, Galveston, Texas
  • Gabriela A. Kulp
    Ophthal & Visual Sciences,
    Univ of Texas Medical Branch, Galveston, Texas
  • Tomasz Wiraszka
    Ophthal & Visual Sciences,
    Univ of Texas Medical Branch, Galveston, Texas
  • Edward R. Kraft
    Anesthesiology,
    Univ of Texas Medical Branch, Galveston, Texas
  • Aristides R. Koutrouvelis
    Anesthesiology,
    Univ of Texas Medical Branch, Galveston, Texas
  • Footnotes
    Commercial Relationships  Bernard F. Godley, inventor (P); Gabriela A. Kulp, inventor (P); Tomasz Wiraszka, None; Edward R. Kraft, inventor (P); Aristides R. Koutrouvelis, inventor (P)
  • Footnotes
    Support  Texas Ignition Fund, research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3238. doi:https://doi.org/
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      Bernard F. Godley, Gabriela A. Kulp, Tomasz Wiraszka, Edward R. Kraft, Aristides R. Koutrouvelis; Non-invasive Delivery Of Human Insulin Into The Posterior Segment Of The Rabbit Eye Using Photokinetic Transscleral Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3238. doi: https://doi.org/.

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

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Abstract

Purpose: : Intravitreal needle injection is associated with risks of retinal detachment and infection. The purpose of this study was to determine the feasibility of a novel platform photokinetic technology to deliver drugs into posterior segment of the eye in a noninvasive fashion and assess the degree of irritation from the procedure.

Methods: : In vivo transscleral permeation studies were performed using New Zealand white and Dutch belted rabbits. Human insulin was formulated in a gel containing various concentrations of drug and hyaluronic acid as vehicle and was delivered using a bench built prototype consisting of a 405 nm LED pulsed at 100 cps, embedded in a silicone scleral shell. Treatment was applied for 1 hour, followed by euthanasia, enucleation of both eyes, separation of different of tissue layers and measurement of human insulin content. Eye irritation was assessed via serial slit lamp exams and quantified using modified McDonald-Shaddock system. Tissues were collected for hematoxilyn/eosin staining.

Results: : Human insulin was detected in all tissue layers in the treated eye and to a lesser extent in the contralateral eye in both pigmented and non-pigmented animals. The levels varied by tissue type; the average % of donor insulin recovered in the rabbit were 25.5 ± 3 and 30.8 ±8 respectively. There were no significant differences between the 2 groups in ocular tissue drug distribution. Human insulin was also detected in rabbit serum, up to 11±2 µU/ml.Superficial corneal epithelial defects were the most severe lesions observed and resolved spontaneously by the end of the study. Our experiment did not reveal significant differences in the irritation scores between exposed and unexposed eyes at any time points, up to 96 hours. Similarly, no morphological differences were observed in tissue sections.

Conclusions: : Our experiments showed that human insulin can be delivered successfully to different eye tissues in a noninvasive fashion using PTD. Permeation of insulin into rabbit eye was not affected by pigmentation. Insulin delivery into the rabbit eye was accomplished without significant damage to the eye. PTD may be an alternative approach for posterior segment drug delivery which avoids the disadvantages of intravitreal needle injection.

Keywords: drug toxicity/drug effects • ocular irritancy/toxicity testing • sclera 
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