D'Angelo Davide, Quarta Eride, Glieca Stefania, Varacca Giada, Flammini Lisa, Bertoni Simona, Brandolini Martina, Sambri Vittorio, Grumiro Laura, Gatti Giulia, Dirani Giorgio, Taddei Francesca, Bianchera Annalisa, Sonvico Fabio, Bettini Ruggero, Buttini Francesca
Food and Drug Department, University of Parma, Parco Area delle Scienze 27a, 43124 Parma, Italy.
Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, 40138 Bologna, Italy.
Pharmaceutics. 2023 Mar 22;15(3):1023. doi: 10.3390/pharmaceutics15031023.
This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder's critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (/) in the feedstock solution and 20% (/ of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.
这项工作阐述了一种用于预防肺移植后排斥反应及治疗新冠肺炎的环孢素 A 干粉吸入剂的研发情况。研究了辅料对喷雾干燥粉末关键质量属性的影响。从原料溶液中乙醇浓度为 45%（/）和甘露醇为 20%（/）开始，获得了在溶解时间和可吸入性方面表现最佳的粉末。该粉末显示出比难溶性原料更快的溶解曲线（威布尔溶解时间为 59.5 分钟，而难溶性原料为 169.0 分钟）。该粉末的细颗粒部分为 66.5%，质量中值空气动力学直径为 2.97 µm。当在 A549 和 THP - 1 细胞上进行测试时，该可吸入粉末在浓度高达 10 µg/mL 时未显示出细胞毒性作用。此外，当在 A549/THP - 1 共培养物上进行测试时，环孢素 A 吸入粉末在降低白细胞介素 - 6 方面显示出效果。当采用感染后或同时治疗方式测试环孢素 A 粉末时，观察到其对 Vero E6 细胞上的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）复制有抑制作用。这种制剂可能代表一种预防肺排斥的治疗策略，但也是一种抑制 SARS-CoV-2 复制和新冠肺炎肺部炎症过程的可行方法。
