Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics

Pharmaceutics

Nikita Jain¹  Suraj Abraham¹  Anitha Thomas¹  Gustavo Lou²  Gavin W. Halbert²  Yvonne Perrie²  Carla B. Roces² 

[1] Precision NanoSystems Inc., 50 655 W Kent Ave N, Vancouver, BC V6P 6T7, Canada;Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK;

关键词: microfluidics;    RNA;    lipid nanoparticles;    manufacture;    critical process parameters;    nucleic acid;   

DOI  :  10.3390/pharmaceutics12111095

来源: DOAJ

【 摘 要 】

In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its scalability, reproducibility and fast preparation. Thus, in this study, we have evaluated operating and formulation parameters to be considered when developing LNPs. Among them, the flow rate ratio (FRR) and the total flow rate (TFR) have been shown to significantly influence the physicochemical characteristics of the produced particles. In particular, increasing the TFR or increasing the FRR decreased the particle size. The amino lipid choice (cationic—DOTAP and DDAB; ionisable—MC3), buffer choice (citrate buffer pH 6 or TRIS pH 7.4) and type of nucleic acid payload (PolyA, ssDNA or mRNA) have also been shown to have an impact on the characteristics of these LNPs. LNPs were shown to have a high (>90%) loading in all cases and were below 100 nm with a low polydispersity index (≤0.25). The results within this paper could be used as a guide for the development and scalable manufacture of LNP systems using microfluidics.

【 授权许可】

Unknown