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

肺部是一个有吸引力但具有挑战性的药物输送靶点。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，可以保护身体免受有害吸入物质的伤害。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肺部给药至关重要。然而，由于人肺和动物肺之间的显著差异，使用活体模型进行肺部给药的临床前开发并不是非常有效。基于Transwell的体外肺模型的屏障功能通常依赖于Transwell植入支架的力学性能，这与临床意义相去甚远。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。准活体系统是Kirkstall公司开发的一种基于Transwell的体外培养系统。该系统允许动态灌流。Chandorkar等人最近开发了一种使用该技术的肺/免疫细胞共培养模型。并显示出更好的呼吸道细胞发育和改善屏障功能。

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.