Centre of Marine Sciences (CCMAR/CIMAR LA), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal.
University of Lisbon, Instituto Superior Técnico, Centro de Química Estrutural, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
Eur J Pharm Sci. 2024 Jun 1;197:106775. doi: 10.1016/j.ejps.2024.106775. Epub 2024 Apr 20.
Research on pharmaceutical dry powders has been increasing worldwide, along with increased therapeutic strategies for an application through the pulmonary or the nasal routes. In vitro methodologies and tests that mimic the respiratory environment and the process of inhalation itself are, thus, essential. The literature frequently reports cell-based in vitro assays that involve testing the dry powders in suspension. This experimental setting is not adequate, as both the lung and the nasal cavity are devoid of abundant liquid. However, devices that permit powder insufflation over cells in culture are either scarce or technically complex and expensive, which is not feasible in early stages of research. In this context, this work proposes the development of a device that allows the delivery of dry powders onto cell surfaces, thus simulating inhalation more appropriately. Subsequently, a quartz crystal microbalance (QCM) was used to establish a technique enabling the determination of dry powder deposition profiles. Additionally, the determination of the viability of respiratory cells (A549) after the insufflation of a dry powder using the developed device was performed. In all, a prototype for dry powder insufflation was designed and developed, using 3D printing methods for its production. It allowed the homogenous dispersion of the insufflated powders over a petri dish and a QCM crystal, and a more detailed study on how dry powders disperse over the supports. The device, already protected by a patent, still requires further improvement, especially regarding the method for powder weighing and the efficiency of the insufflation process, which is being addressed. The impact of insufflation of air and of locust bean gum (LBG)-based microparticles revealed absence of cytotoxic effect, as cell viability roughly above 70 % was always determined.
药物干粉的研究在全球范围内不断增加，同时也增加了通过肺部或鼻腔途径应用的治疗策略。因此，模拟呼吸环境和吸入过程本身的体外方法和测试是必不可少的。文献经常报告基于细胞的体外测定，涉及干粉在悬浮液中的测试。这种实验设置是不充分的，因为肺部和鼻腔都没有大量的液体。然而，允许在培养细胞上进行粉末喷射的设备要么稀缺，要么技术复杂且昂贵，这在研究的早期阶段是不可行的。在这种情况下，这项工作提出了开发一种允许将干粉输送到细胞表面的设备，从而更适当地模拟吸入。随后，使用石英晶体微天平 (QCM) 建立了一种能够确定干粉沉积轮廓的技术。此外，使用开发的设备测定了在吸入干粉后呼吸细胞 (A549) 的活力。总之，使用 3D 打印方法设计和开发了一种干粉喷射的原型，允许在培养皿和 QCM 晶体上均匀分散喷射的粉末，并更详细地研究干粉如何在载体上分散。该设备已获得专利保护，但仍需要进一步改进，特别是关于粉末称重方法和喷射过程效率的改进，目前正在解决这些问题。空气和槐豆胶（LBG）基微球的喷射的影响揭示了无细胞毒性作用，因为细胞活力总是大致在 70%以上。
