An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro

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...

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Published in:Pharmaceutics 2023-03, Vol.15 (3), p.1023
Main Authors: 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
Format: Article
Language:English
Subjects:
Coronaviruses
COVID-19
Cyclosporine
cyclosporine-A
cytokine storm
Design of experiments
Dosage and administration
Drug dosages
Drug therapy
dry powder inhaler
Ethanol
Graft versus host reaction
Immune system
Inhalers
Lung transplants
Lungs
Metabolism
Peptides
Prevention
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
spray-drying
transplant rejection
Transplantation
Variance analysis
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15031023