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局部治疗溃疡性结肠炎的替代发泡剂。

Alternative foaming agents for topical treatment of ulcerative colitis.

机构信息

Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa, 50011.

出版信息

J Biomed Mater Res A. 2018 May;106(5):1448-1456. doi: 10.1002/jbm.a.36324. Epub 2018 Jan 24.

Abstract

Approximately 907,000 Americans currently suffer from ulcerative colitis, a condition characterized by inflammation of the large intestine or rectum. Treatment of this disease often includes anti-inflammatory medication or immunosuppressants. Here foams are an attractive delivery platform, offering relatively high bioavailability, low systemic exposure, and improved patient comfort. However, the surfactants that generate these foams may adversely affect the diseased mucosa. Therefore, this project evaluated two alternative surfactants for use in topical drug delivery platforms: sodium caseinate and l-α-phosphatidylcholine. Both were compared to the biocompatible surfactant Pluronic F-127 using stability and density tests, and biocompatibility tests performed on mini-guts. Sodium caseinate foams were less stable but denser than Pluronic foams; however, they exhibited an unexpectedly low shelf-life. l-α-phosphatidylcholine was an unsuccessful primary foaming agent owing to poor foamability at low concentrations. Mini-gut growth rates were not significantly altered by surfactants, while morphology and an MTT assay identified Pluronic as the most biocompatible surfactant at higher concentrations. These results clarify the possible challenges that the tested surfactants may present in topical delivery platforms and show the relevance of permeability to tissue-surfactant interaction tests. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1448-1456, 2018.

摘要

目前,约有 907,000 名美国人患有溃疡性结肠炎,这是一种以大肠或直肠炎症为特征的疾病。这种疾病的治疗通常包括抗炎药物或免疫抑制剂。在这里,泡沫是一种有吸引力的给药平台,提供相对较高的生物利用度、低全身暴露和改善的患者舒适度。然而,产生这些泡沫的表面活性剂可能会对患病的粘膜产生不利影响。因此,本项目评估了两种替代表面活性剂用于局部药物递送平台:酪蛋白酸钠和 l-α-磷脂酰胆碱。稳定性和密度测试比较了这两种与生物相容的表面活性剂 Pluronic F-127,以及在迷你肠道上进行的生物相容性测试。酪蛋白酸钠泡沫的稳定性较低,但密度高于 Pluronic 泡沫;然而,它们表现出出乎意料的低保质期。l-α-磷脂酰胆碱由于在低浓度下的起泡性差,是一种不成功的主要发泡剂。表面活性剂对迷你肠道的生长速度没有显著影响,而形态和 MTT 测定表明 Pluronic 在较高浓度下是最具生物相容性的表面活性剂。这些结果阐明了测试表面活性剂在局部递送平台中可能存在的挑战,并表明对组织-表面活性剂相互作用测试的通透性具有相关性。© 2018 威利父子公司

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