Impact of Crystalline and Amorphous Matrices on Successful Spray Drying of siRNA Polyplexes for Inhalation of Nano‐in‐Microparticles

Autor: Aditi Mehta, Tobias W. M. Keil, Olivia M. Merkel, Domizia Baldassi, Wolfgang Friess, Christoph M Zimmermann, Friederike Adams
Rok vydání: 2021
Předmět:
Zdroj: Advanced Therapeutics
Adv Ther (Weinh)
ISSN: 2366-3987
DOI: 10.1002/adtp.202100073
Popis: To develop stable and inhalable dry powder formulations with long shelf life, we spray dried polyplexes consisting of siRNA and a polyethylenimine based block copolymer in presence of mannitol or trehalose. We investigated the effect of inlet (T-In) and outlet (T-Out) temperature on the recovery of siRNA as well as adsorption effects within the tubing material. Choosing a low abrasion silicon tubing prevented siRNA loss due to adsorption. Mannitol and trehalose formulations preserved siRNA integrity regardless of excipient concentration and temperature at T-Out below the siRNA melting temperature. Trehalose formulations allowed full siRNA recovery whereas mannitol formulations resulted in spray drying induced losses of ~20 % siRNA and of 50-60 % polymer. Mannitol formulations showed optimal aerodynamic characteristics as confirmed by next generation impaction analysis based upon siRNA content. All spray dried formulations resulted in GFP silencing comparable or better than freshly prepared polyplexes. To test if the observed results could be transferred, formulations of siRNA and transferrin-PEI conjugates were spray dried, characterized and used to transfect primary human T cells ex vivo. Results confirmed successful silencing of the Th2 transcription factor GATA3 in primary CD4(+) T cells with spray dried formulations as a potential treatment for severe asthma.
Databáze: OpenAIRE
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