Ocular distribution of the chimeric protein IL2-PE40

Abstract

A construct of IL-2 and pseudomonas exotoxin (PE40) has been genetically engineered. An aliquot of 100 microliter of the chimeric protein, radiolabelled with I125, was administered to healthy rats by various routes. At different intervals, ocular and non ocular tissues were removed and the levels of the radiolabelled chimeric protein IL-2-PE40 measured. Systemic administration of IL2-PE40 either intravenously (IV) or intraperitoneally (IP) leads to high levels of the drug in the blood, liver and spleen. Little or no radioactivity is observed within the ocular tissues using this route. On the other hand, local administration of the drug either as subtenon injection or as eye drops resulted in a very high concentration of the drug within the conjunctiva, cornea and sclera, with little radioactivity detected systemically. Subtenon injection induced a significant drug level within the optic nerve. With the drops, the chimeric protein was also detected, in low levels, intraocularly.

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Intravital Multiphoton Microscopy of the Ocular Surface: Alterations in Conventional Dendritic Cell Morphology and Kinetics in Dry Eye Disease

“…Considering that the cornea is an avascular tissue, systemic administration of large molecules, such as antibodies, does not allow labeling of the corneal structures (87)(88)(89). Similarly, subconjunctival injection of antibodies generally does not lead to proper labeling of all corneal structures, such as the epithelium (90), in which a subset of immune cells reside.…”

Human toxin-based recombinant immunotoxins/chimeric proteins as a drug delivery system for targeted treatment of human diseases

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