Evaluation of Intracameral Pentablock Copolymer Thermosensitive Gel for Sustained Drug Delivery to the Anterior Chamber of the Eye

被引:6
|
作者
Schaefer, Elizabeth [1 ]
Smith, Sara M. [1 ]
Salmon, Jacklyn [1 ]
Abbaraju, Santhi [2 ]
Amin, Rasidul [2 ]
Weiss, Sidney [3 ]
Grau, Ulrich [3 ]
Velagaleti, Poonam [3 ]
Gilger, Brian [1 ,3 ]
机构
[1] North Carolina State Univ, Lab Ocular Toxicol Immunol & Drug Delivery, 1060 William Moore Dr, Raleigh, NC 27607 USA
[2] Symmetry Biosci, Res Triangle Pk, NC USA
[3] I Novion Inc, Randolph, NJ USA
关键词
ocular; sustained drug delivery; intracameral; pentablock; copolymer; RELEASE; PLGA; DEGRADATION; PROTEINS;
D O I
10.1089/jop.2016.0181
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To investigate PTSgels (Pentablock copolymers) as an injectable formulation technology for sustained ocular drug delivery. Drug release profile, tolerability, and polymer degradation for one of the thermosensitive, biodegradable, and biocompatible compositions were investigated through intracameral (IC) injection in rabbits. Methods: New Zealand White rabbit eyes were injected IC (50L) with 100g near-infrared-immunoglobulin G (NIR-IgG) in balanced salt solution (BSS) or 20% PTSgel; or with PTSgel or BSS alone. Ocular irritation scoring, intraocular pressure (IOP), and corneal thickness (CT) measurement, as well as color and infrared photography, were performed for up to 28 days postinjection. Upon euthanasia at 7, 14, or 28 days, eyes underwent ex vivo imaging (Xenogen IVIS) followed by tissue fixation and histopathology. Results: IC injection of PTSgel (liquid at room temperature) was performed without difficulty using a 31G needle. The polymer quickly gelled in the IC space resulting in an inferior anterior chamber deposit. The tested PTSgel was well tolerated, with no significant changes in IOP or CT. Eyes injected with NIR-IgG in PTSgel had visible NIR-IgG through 9 days postinjection, and ex vivo imaging detected a strong NIR-IgG signal in the anterior chamber through day 28. The gel deposit steadily decreased in size over time and was nearly eliminated by 28 days. Conclusions: The PTSgel released IgG for 28 days and was well tolerated. The polymer degraded in parallel with drug release. These results demonstrate the potential of intracameral PTSgel formulations for sustained delivery of biologic therapies to the ocular anterior segment.
引用
收藏
页码:353 / 360
页数:8
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