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用于递送激活素受体样激酶 5 抑制剂 SB-505124 的热可逆凝胶在青光眼滤过手术中的应用。

Thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery.

机构信息

Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.

出版信息

Pharm Dev Technol. 2013 Jul-Aug;18(4):957-62. doi: 10.3109/10837450.2011.647035. Epub 2011 Dec 30.

Abstract

The purpose of this study is to investigate a thermoreversible gel using Pluronic F-127 to deliver an activin receptor-like kinase 5 (ALK-5) inhibitor SB-505124 in glaucoma filtration surgery (GFS). The gel was characterized for in vitro drug release and viscosity studies. Cytotoxicity of Pluronic F-127 was examined by MTT assay using cultured rabbit subconjunctival fibroblasts. In addition, Pluronic F-127 gel (18% w/v) containing 5 mg of SB-505124 was applied at the surgical site in an in vivo rabbit GFS model. In the in vitro viscosity study, the gel showed a change in viscosity (from 1000 cps to 45,000 cps) from low temperature (10°C) to body temperature (37°C). The in vitro drug release study demonstrated 100% drug release within 12 h. The gel did not show cytotoxicity to the cultured rabbit subconjunctival cells by MTT assay. In the in vivo rabbit GFS model, the drug was successfully delivered by injection and no severe post-surgical complications were observed. A thermoreversible gel system with SB-505124 was successfully prepared and delivered for the rabbit GFS model, and it may provide a novel delivery system in GFS.

摘要

本研究旨在利用 Pluronic F-127 研制一种温敏凝胶,以在青光眼滤过手术(GFS)中递送激活素受体样激酶 5(ALK-5)抑制剂 SB-505124。对凝胶进行了体外药物释放和黏度研究。通过 MTT 法检测了培养的兔眼结膜下成纤维细胞的 Pluronic F-127 的细胞毒性。此外,在体内兔 GFS 模型中,将含有 5mg SB-505124 的 Pluronic F-127 凝胶(18%w/v)应用于手术部位。在体外黏度研究中,凝胶从低温(10°C)到体温(37°C)表现出黏度(从 1000cps 变为 45000cps)的变化。体外药物释放研究表明,在 12 小时内可实现 100%的药物释放。MTT 法检测表明,凝胶对培养的兔眼结膜下细胞无细胞毒性。在体内兔 GFS 模型中,通过注射成功递送了药物,且未观察到严重的术后并发症。成功制备并递送给兔 GFS 模型的具有 SB-505124 的温敏凝胶系统,可能为 GFS 提供了一种新的递送系统。

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