Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics.

Pharmaceutics
Carla B RocesYvonne Perrie

Abstract

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.

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Citations

Jan 6, 2021·Advanced Drug Delivery Reviews·Jeonghwan KimGaurav Sahay
Feb 28, 2021·International Journal of Pharmaceutics·Yuchen FanKelly Zhang
Apr 13, 2021·Advanced Drug Delivery Reviews·Dongmei CunMingshi Yang
May 30, 2021·Colloids and Surfaces. B, Biointerfaces·Paulina Skupin-MrugalskaHanna Piotrowska-Kempisty
Jun 3, 2021·Diagnostics·Yun-Siang LinChen-Fu Chien
Jul 3, 2021·International Journal of Molecular Sciences·Olga SergeevaTimofei Zatsepin
Jun 8, 2021·International Journal of Pharmaceutics·Xiaojing LiuDaniel Scherman
Aug 29, 2021·Pharmaceutics·Erica QuagliariniGiulio Caracciolo

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Methods Mentioned

BETA
dynamic light scattering
Fluorescence
RNA Assay

Software Mentioned

Zetasizer

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