Inhalable cyclosporine powder for the prevention of pulmonary rejection and the treatment of Covid-19
Davide D’Angelo1, Eride Quarta1, Martina Brandolini2, Vittorio Sambri2, Lisa Flammini1, Simona Bertoni1, Fabio Sonvico1 & Francesca Buttini1
1Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
2Microbiology Unit, The Great Romagna Area Hub Laboratory, 47522 Pievesestina, Cesena, Italy.
Summary
The work describes the formulation of a powder for inhalation containing Cyclosporine_A (CsA), a peptide with low water solubility. The formulation was designed to reduce the dose of CsA to be administered following lung transplantation and potentially against SARS-CoV-2 replication and in the containment of the inflammatory process associated with Covid-19.
The powder was obtained through a spray drying process and mannitol was chosen as bulk excipient to improve the respirability and solubility of the CsA. Dissolution, studied using Respicell TM apparatus, showed a faster profile for the spray-dried powder compared to the raw material. The CsA powder was found to be highly respirable (MMAD of 1.38 µm and FPF 83.3%). In vitro analysis on A549 and THP-1 cell lines did not indicate any cytotoxic effect and the anti-inflammatory effect was maintained even after the spray drying process. This study also highlights the efficacy of cyclosporine against the omicron BA.1 variant of SARS-CoV-2, opening the possibility of using this formulation with a low dose in the treatment of Covid 19.
Key Message
This work led to the production of a CsA inhalation powder. The powder showed excellent aerodynamic characteristics and a better dissolution profile than the raw material maintained its anti-inflammatory activity even after the spray drying process and demonstrated antiviral activity against SARS-CoV-2 variant Omicron AB.1.