从鼻子组织到芯片上的鼻子粘液的路径:第2部分 - - 药物吸收测试的先进微流体鼻子体外模型
Eugen Viktor Koch1,2, Sebastian Bendas2,3, Kristina Nehlsen4
1Institute of Microtechnology, TU Braunschweig, Alte Salzdahlumer Str. 203, 38124 Braunschweig, Germany.
Pharmaceutics
|October 28, 2023
概括
研究人员在芯片平台上开发了一种新的鼻腔粘膜,用于药物输送研究. 这种仿生系统增强了乳毛形成和粘液分布,有助于临床前药物测试.
科学领域:
- 生物医学工程 生物医学工程
- 药理学 药理学是指药理学的学科.
- 药物输送系统 药物输送系统
背景情况:
- 鼻腔粘膜提供了一个有前途的系统药物管理路线,因为它的可访问性和血管化.
- 身体障碍,如粘膜清除,对药物候选者在鼻腔药物输送中构成重大挑战.
- 有效的临床前测试模型对于评估通过鼻腔粘膜的药物透性和疗效至关重要.
研究的目的:
- 开发和验证一种新的微流体芯片平台,模仿人类鼻腔粘膜,用于药物透性研究.
- 评估微流体鼻腔粘膜模型在粘液层形成和纤毛功能方面的生理相关性.
- 评估该平台在临床前环境中确定药物透系数的实用性.
主要方法:
- 生物模拟玻璃芯片的微制造,具有控制的双向空气流,以模拟生理剪切应力.
- 开发一种膜转移技术,用于预培养一种已不朽的猪鼻上皮细胞层.
- 在微流体芯片内进行动态培养,评估粘液分布和乳毛形成.
- 使用微粒子图像速度计记录状运输机制.
- 使用FITC-dextran 4000进行透研究以确定透系数.
主要成果:
- 在微流体芯片中的动态培养导致了均的粘液膜分布,并且与静态条件相比,乳毛形成显著增加.
- 通过微粒子图像速度测量,成功记录了状运输机制.
- 芯片模型上的鼻腔粘膜证明了适合透研究的适用性,产生了与已建立的体外和体外模型相比的透系数.
- 开发的平台为研究鼻腔药物吸收提供了更具生理相关性的环境.
结论:
- 这种新型的微流体鼻膜平台有效地复制了鼻上皮的关键生理特征,包括粘液层和纤毛功能.
- 这种"芯片上的鼻腔粘膜"系统是临床前药物透研究的宝贵工具,可以更准确地评估药物输送潜力.
- 该平台对未来的自动化和应用充满希望,作为制药研发的非动物替代品.
相关概念视频
01:16Methods for Studying Drug Absorption: In vitro
236
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
236
01:09Methods for Studying Drug Absorption: In situ
244
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
244