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Elizabeth Schaefer, Jacklyn H Salmon, Santhi Abbaraju, Rasidul Amin, Sidney L Weiss, Ulrich M Grau, Poonam Velagaleti, Brian C Gilger; Sustained IgG delivery to the anterior chamber of rabbits using pentablock co-polymers. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5712.
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© ARVO (1962-2015); The Authors (2016-present)
With the increasing development of immunotherapies, sustained antibody delivery to the ocular anterior segment could prove beneficial for many common ocular diseases. The purpose of this study was to evaluate sustained antibody delivery using pentablock co-polymer (PBC), injected intracamerally (IC) in the normal rabbit.
New Zealand White rabbits were injected IC (50ul, 27g needle) with either BSS, 100ug of near infrared dye (NIR) labeled IgG in BSS, 20% PBC, or 100ug of NIR IgG in 20% PBC. Hackett-McDonald ocular irritation scoring, intraocular pressure (IOP), central corneal pachymetry (CT), and color and infrared photography were performed at 0, 1, 2, 3, 5, 7, 9, 14, 21, and 28 days post injection. At 7, 14, and 28 days, rabbits were euthanized. The eyes were collected and immediately imaged by ex vivo imaging (Xenogen IVIS). The eyes were then either frozen for tissue dissection or processed for histopathology. Serum for measurement of NIR IgG concentrations was collected at 0, 7, 14, and 28 days.
IC injection of PBC was performed without difficulty, was well tolerated, and no significant difference in IOP or CT was observed between treatments. All eyes developed a mild, transient inflammatory response following injection. PBC gel was visible as a focal deposit in the inferior anterior chamber in all eyes injected with PBC by day 1. The deposit steadily decreased in size over time and was nearly eliminated by 28 days. On infrared photography, the NIR IgG was visible as granular deposits in the anterior chamber. In eyes injected with NIR BSS, the IgG was visible immediately after injection and was negative by 24 hours; eyes with NIR IgG in PBC had visible NIR IgG through 9 days post injection. No NIR IgG was visible in eyes with only BSS or PBC. Ex vivo imaging revealed a strong signal of NIR IgG in the anterior chamber of eyes injected with NIR IgG in PBC through day 28; no signal was detected in eyes receiving NIR IgG in BSS or those with only PBC or BSS. Serum levels of NIR IgG were below level of detection for each time measured.
PBC compositions can be tailored for a variety of applications. The PBC composition used in this study was well tolerated, provided sustained release of IgG, and was largely eliminated from the anterior chamber by 28 days. These results support the further study of PBCs for sustained delivery of therapies for ocular anterior segment diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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