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S. Molokhia, X. Liu, E. Jeong, W. Higuchi, K. Li; Transscleral Iontophoretic Delivery of a Macromolecule in vivo. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1814.
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The objective was to study the delivery of a high molecular weight compound surrogate to clinical therapeutic agents using transscleral iontophoretic delivery in vivo.
Transscleral passive and iontophoretic delivery and intravitreal injection were conducted using male New Zealand White rabbits in vivo. All animals were used in compliance with the ARVO statement for the use of animals in Ophthalmic and Vision Research. Constant current cathodal iontophoresis of 4 mA was conducted at the sclera near the limbus under the upper eyelid. Passive delivery without an electric field was performed as a control. GalbuminTM (Gd-labeled albumin) was the model permeant used in the present study. Nuclear magnetic resonance imaging (MRI) was used to monitor the distribution of the molecule in the eye after ocular delivery in vivo. In addition, tissue extractions of conjunctiva, sclera, and retina were also conducted in the transscleral iontophoresis study to determine the amount of GalbuminTM in the eye tissues using ICP-OES.
GalbuminTM was mainly delivered within 60 minutes after iontophoresis into the conjunctiva and sclera in microgram quantities in vivo. The molecule was observed to diffuse towards the posterior tissues in the upper hemisphere of the eye within a 12-hr time span. Passive transscleral delivery was minimal compared to transscleral iontophoresis. Intravitreal injection of the molecule showed longer t1/2 than that of transscleral iontophoresis.
The results suggest the potential of transscleral iontophoresis to be a non-invasive delivery method for therapeutic large molecules.
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