A dry powder formulation for peripheral lung delivery and absorption of an anti-SARS-CoV-2 ACE2 decoy polypeptide
One of the strategies proposed for the neutralization of SARS-CoV-2 has been to synthetize small proteins able to act as a decoy towards the virus spike protein, preventing it from entering the host cells. In this work, the incorporation of one of these proteins, LCB1, within a spray-dried formulation for inhalation was investigated. A design of experiments approach was applied to investigate the optimal condition for the manufacturing of an inhalable powder. The lead formulation, containing 6% w/w of LCB1 as well as trehalose and L-leucine as excipients, preserved the physical stability of the protein and its ability to neutralize the virus.
In addition, the powder had a fine particle fraction of 58.6% and a very high extra-fine particle fraction (31.3%) which could allow a peripheral deposition in the lung. The in vivo administration of the powder showed no significant difference in the pharmacokinetic from the liquid formulation, indicating the rapid dissolution of the microparticles and its capability to translocate into the plasma. Moreover, LCB1 in plasma samples still maintained the ability to neutralize the virus. In conclusion, the optimized spray drying conditions allowed to obtain an inhalation powder able to preserve the protein biological activity, rendering it suitable for a systemic prevention of the viral infection via pulmonary administration
Download the full article as PDF here A dry powder formulation for peripheral lung delivery and absorption of an anti-SARS-CoV-2 ACE2 decoy polypeptide
or read it here
Materials
Trehalose (batch no. 07/4801) and L-leucine (batch no. Q0096002) were purchased from A.C.E.F. Spa (Italy) and mannitol as Pearlitol 50C (batch no. e 869 K) from Roquette (France). Lactose (Respitose SV003, batch no. 10258398) was purchased from DMV International (Netherlands), and glycine (lot #SLCC7952) from Sigma-Aldrich (USA). Ultrapure water (0.055 µS/cm) was produced by reverse osmosis (PureLab Pulse, Elga-Veolia, Italy).
Stefania Glieca, Davide Cavazzini, Elisabetta Levati, Valentina Garrapa, Angelo Bolchi, Valentina Franceschi, Simone Odau, Simone Ottonello, Gaetano Donofrio, Jonas Füner, Fabio Sonvico, Ruggero Bettini, Barbara Montanini, Francesca Buttini, A dry powder formulation for peripheral lung delivery and absorption of an anti-SARS-CoV-2 ACE2 decoy polypeptide, European Journal of Pharmaceutical Sciences, 2023, 106609, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2023.106609.
See the webinar:
“Rational Selection of Cyclodextrins for the Solubilization of Poorly Soluble Oral Drugs”, 8. November 2023:
Get more information & register here for free:
