Spray drying of mRNA lipoplexes to produce an inhalable dry powder formulation for mRNA therapeutics
Jana Schembera1, Ricarda Leister2, Constanze Müller2 and Regina Scherließ1
1Department of Pharmaceutics and Biopharmaceutics, Kiel University, Gutenbergstrasse 76, 24118 Kiel, Germany
2Meggle GmbH & Co. KG, Megglestr. 6-12, 83512 Wasserburg am Inn, Germany
Summary
This project aims to develop an inhalable dry powder platform for mRNA therapeutics. To create this dry powder formulation, we utilised lipoplexes containing mRNA and DOTAP:DOPE and conducted spray drying experiments using mannitol as a matrix. Lower outlet temperatures preserved transfection efficiency better than higher outlet temperatures. After redispersion of the spray dried powder, the z-average and zeta potential indicated stable nanoparticles within the desired size range for all used outlet temperatures. The aerodynamic characterisation of the spray dried powder showed a moderate fine particle fraction (approx. 35%) using the RS01 DPI as device. However, a considerable amount of powder remained in the capsules and the throat. In a first attempt, lactose sweeper crystals were introduced as a potential solution to enhance particle detachment. The sweeper crystals did not affect the fine particle fraction in this study, while they tend to increase the delivered dose. Further research is required to improve the composition of the sweeper crystal blends and explore alternative strategies to tune aerodynamic performance.