March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Transscleral Iontophoretic Delivery of a Macromolecule into the Rabbit Eye
Author Affiliations & Notes
  • John Higuchi
    Aciont Inc, Salt Lake City, Utah
  • Kongnara Papangkorn
    Aciont Inc, Salt Lake City, Utah
    University of Utah, Salt Lake City, Utah
  • Sarah Molokhia
    University of Utah, Salt Lake City, Utah
  • Donald Mix
    Aciont Inc, Salt Lake City, Utah
  • Charlotte Butler
    Aciont Inc, Salt Lake City, Utah
  • Prasoona Karra
    Aciont Inc, Salt Lake City, Utah
  • Balbir Brar
    Aciont Inc, Salt Lake City, Utah
  • S. Kevin Li
    Aciont Inc, Salt Lake City, Utah
    University of Cincinnati, Cincinnati, Ohio
  • William I. Higuchi
    Aciont Inc, Salt Lake City, Utah
    University of Utah, Salt Lake City, Utah
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 464. doi:
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      John Higuchi, Kongnara Papangkorn, Sarah Molokhia, Donald Mix, Charlotte Butler, Prasoona Karra, Balbir Brar, S. Kevin Li, William I. Higuchi; Transscleral Iontophoretic Delivery of a Macromolecule into the Rabbit Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):464.

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

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Abstract

Purpose: : To study the in vivo transscleral anodal iontophoresis (AI) delivery of Immunoglobulin G (IgG, MW~150 kDa and a surrogate for bevacizumab) and to evaluate key iontophoretic conditions (i.e., current, current density, and drug solution volume) on the amount and distribution of IgG delivered into the eye.

Methods: : AI was performed on New Zealand White rabbits using a Visulex system containing IgG (2.5%). There were 4 groups of rabbits (n=3 for each group) under 4 different conditions of AI. After 20 min of AI delivery, the rabbits were sacrificed and the eyes were enucleated. The eyes were dissected and the cornea, aqueous humor, vitreous, conjunctiva, sclera, choroid and retina analyzed for IgG content by ELISA.

Results: : At 4 mA (current density = 1.8 mA/cm2), the total amount IgG delivered was 438 ± 63 and 364 ± 27 µg with 400 µL and 200 µL IgG solution volumes in Visulex system, respectively. At 8 mA (current density = 3.6 mA/cm2), the total amount IgG delivered was 727 ± 38 and 457 ± 94 µg with 400 µL and 200 µL solution volumes, respectively. With regard to tissue distributions, at both current densities, most of the IgG was found in the conjunctiva and sclera at amounts roughly in proportion to their total amounts at the two current densities. There were significant amounts of IgG found in the deeper tissues, including the retina/choroid. It was interesting to find that the average amounts in the deeper tissues (e.g., retina/choroid and vitreous) were much higher at the higher current density relative to the total amounts (e.g., 8 vs 42 µg for the retina/choroid).

Conclusions: : This study might be the first to demonstrate successful noninvasive macromolecule delivery in vivo to the posterior eye tissues with the amounts of IgG delivered being of the same order of magnitude of that used in the intravitreal injection of Avastin. It was estimated that iontophoretic delivery of IgG is approximately 1000-fold superior over passive. The reproducibility was found to be quite satisfactory (5-20%). The volume of drug solution used as well as current density appears to be significant in AI drug delivery efficiency for both amounts and depth of penetration.

Keywords: age-related macular degeneration • vascular endothelial growth factor • drug toxicity/drug effects 
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