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Developing PHA-based biomaterials for pulmonary drug delivery on advanced 3D lung/immune cell models (Industry Project) KIRKSTALL

在先进的 3D 肺/免疫细胞模型上开发用于肺部药物输送的基于 PHA 的生物材料（行业项目）KIRKSTALL

基本信息

批准号：
2891072
负责人：
金额：
--
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2891072
关键词：
Developing PHA based biomaterials pulmonary

项目摘要

Lung is an attractive but challenging target for drug delivery. The enormous surface area of the lung is well-suited for both topical and systemic absorption of medications. On the other hand, lung has efficient mechanical, chemical, and immunological mechanisms that can protect the body from unwanted inhaled materials. Clinically inhalation has been used as the major route for pulmonary drug administration. Thus, developing less immunogenic vehicles is crucial for pulmonary drug delivery. However, preclinical development of pulmonary drug delivery using in vivo models is not very efficient due to a significant difference between human and animal lungs. The barrier functions from the transwell-based in vitro lung models generally depend on the mechanical properties of the transwell insert scaffolds, which is far from clinically relevant. Therefore, advanced pulmonary models are needed to reflect the alveolar-capillary barrier and the relevant immune response. Quasi Vivo System is an in vitro transwell-based culture systems developed by Kirkstall Ltd. The system allows dynamic perfusion. A lung/immune cell co-culture model using this technology has been recently developed by Chandorkar et al. and showed better airway cell development and improved barrier function.

肺是一个有吸引力但具有挑战性的药物递送靶点。肺的巨大表面积非常适合药物的局部和全身吸收。另一方面，肺具有有效的机械、化学和免疫机制，可以保护身体免受不必要的吸入物质的影响。临床上吸入给药已成为肺部给药的主要途径。因此，开发免疫原性较低的载体对于肺部药物递送至关重要。然而，由于人和动物肺之间的显著差异，使用体内模型的肺部药物递送的临床前开发不是非常有效。基于transwell的体外肺模型的屏障功能通常取决于transwell插入支架的机械性能，这与临床相关性很远。因此，需要先进的肺模型来反映肺泡-毛细血管屏障和相关的免疫反应。Quasi Vivo系统是由Kirkstall有限公司开发的一种基于transwell的体外培养系统，该系统允许动态灌注。使用该技术的肺/免疫细胞共培养模型最近已由Eschorkar等人开发，并显示出更好的气道细胞发育和改善的屏障功能。