N-乙酰半胱氨酸调节粘液对纳米粒子毒性的影响

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2023-09-21 DOI:10.1016/j.ijpx.2023.100212
Enkeleda Meziu , Kristela Shehu , Marcus Koch , Marc Schneider , Annette Kraegeloh
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引用次数: 0

摘要

人类呼吸道粘液是一种生物水凝胶,为下层上皮形成保护屏障。粘液层的调节已被用作增强跨粘膜药物载体运输的策略。然而,这种策略的缺点是粘液屏障特性的潜在降低,特别是在暴露于颗粒物增加的情况下。在这项研究中,我们研究了粘液调节对其保护作用的影响。体外粘液由Calu-3细胞产生,在气液界面培养21天,并用于在细胞顶部形成的进一步测试。共聚焦3D成像数据分析显示,21天后,Calu-3细胞分泌厚度为24±6μm的粘液层。粘液似乎限制了500 nm羧基改性的聚苯乙烯颗粒渗透到层的上部5–10μm。此外,还开发了一种使用雾化N-乙酰半胱氨酸(NAC)的粘液调节方案。这种处理通过NAC的粘液溶解作用增强了颗粒通过粘液向下渗透到更深的层。这些发现得到了细胞毒性数据的支持,表明完整的粘液保护下层上皮免受颗粒诱导的对膜完整性的影响。分别使用50和100nm胺修饰的聚苯乙烯纳米颗粒和50 nm羧基修饰的聚苯乙烯纳米粒子,探讨NAC处理对粘液保护性能的影响。细胞毒性仅由胺修饰颗粒与NAC处理联合诱导,这意味着调节粘液的保护功能降低。总的来说,我们的数据强调了将粘液保护功能的评估纳入粘液调节治疗方法开发的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity

Human respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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