1. An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro
- Author
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Davide D’Angelo, Eride Quarta, Stefania Glieca, Giada Varacca, Lisa Flammini, Simona Bertoni, Martina Brandolini, Vittorio Sambri, Laura Grumiro, Giulia Gatti, Giorgio Dirani, Francesca Taddei, Annalisa Bianchera, Fabio Sonvico, Ruggero Bettini, and Francesca Buttini
- Subjects
cyclosporine-A ,spray-drying ,dry powder inhaler ,SARS-CoV-2 ,cytokine storm ,transplant rejection ,Pharmacy and materia medica ,RS1-441 - Abstract
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% (v/v) in the feedstock solution and 20% (w/w) 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.
- Published
- 2023
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