Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins
Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins
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DOI：
10.1016/s0168-3659(02)00027-5
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发表时间：
2002-04-23
影响因子：
10.8
通讯作者：
Peppas, NA
中科院分区：
文献类型：
--
作者：
Torres-Lugo, M;García, M;Peppas, NA
口服递送具有不利物理化学性质的治疗剂所面临的挑战。例如蛋白质。已经成为设计和开发能够绕过生物屏障的新型口服给药系统的主要动机。在这项工作中，我们研究了复合敏感的水凝胶纳米球组成的聚[甲基丙烯酸接枝聚（乙二醇）]（P（MAA-g-EG）），在一个模型的生物环境。为了这个目的。采用胃肠道细胞培养模型Caco-2细胞系来研究聚合物载体的细胞毒性作用及其对细胞单层完整性的影响。通过比色测定和使用台盼蓝排除法计数活细胞来测定聚合物网络对细胞单层的细胞毒性作用。进行电生理学测量以测量在存在和不存在纳米球悬浮液的情况下单层中的跨上皮电阻变化。P（MAA-g-EG）纳米球系统与Caco-2细胞单层的物理化学相互作用的检查显示，这些系统具有低细胞毒性，并且能够打开上皮细胞之间的紧密连接，因此显著降低跨上皮电阻。(C)2002 Elsevier Science B. V.保留所有权利。
The challenges faced to orally deliver therapeutic agents with unfavorable physicochemical properties. such as proteins. have been the primary motivation for the design and development of novel oral delivery systems that could circumvent biological barriers. In this work, we examined complexation-sensitive hydrogel nanospheres composed of poly [methacrylic acid-grafted-poly(ethylene glycol)] (P(MAA-g-EG)), on a model biological environment. For this purpose. a gastrointestinal cell culture model, the Caco-2 cell line, was employed to investigate the cytotoxic effects of the polymeric carrier and its effects on the cell monolayer integrity. The determination of the cytotoxic effects of the polymer network on the cell monolayer was performed by a colorimetric assay and by the counting of viable cells using the trypan blue exclusion method. Electrophysiological measurements were performed to measure the transepithelial electrical resistance changes in the monolayers in the presence and absence of the nanosphere suspension. The examination of the physicochemical interactions of the P(MAA-g-EG) nanosphere system with Caco-2 cell monolayers revealed that these systems possessed low cytotoxicity and were capable of opening the tight junctions between epithelial cells, therefore significantly reducing the transepithelial electrical resistance. (C) 2002 Elsevier Science B.V. All rights reserved.