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Single pot organic solvent-free thermocycling technology for siRNAionizable LNPs: a proof-of-concept approach for alternative to microfluidics.
- Source :
-
Drug Delivery . Dec2022, Vol. 29 Issue 1, p2644-2657. 14p. - Publication Year :
- 2022
-
Abstract
- Ionizable LNPs are the latest trend in nucleic acid delivery. Microfluidics technology has recently gained interest owing to its rapid mixing, production of nucleic acid-ionizable LNPs, and stability of nucleic acid inside the body. Industrial scale-up, nucleic acid-lipid long-term storage instability, and high production costs prompted scientists to seek alternate solutions to replace microfluidic technology. We proposed a single-pot, organic solvent-free thermocycling technology to efficiently and economically overcome most of the limitations of microfluidic technology. New thermocycling technology needs optimization of process parameters such as sonication duration, cooling-heating cycle, number of thermal cycles, and lipid:aqueous phase ratio to formulate precisely sized particles, effective nucleic acid encapsulation, and better shelf-life stability. Our research led to the formulation of siRNA-ionizable LNPs with particle sizes of 104.2 ± 34.7 nm and PDI 0.111 ± 0.109, with 83.3 ± 4.1% siRNA encapsulation. Thermocycling siRNA-ionizable LNPs had comparable morphological structures with commercialized microfluidics ionizable LNPs imaged by TEM and cryo-TEM. When compared to microfluidics ionizable LNPs, thermocycling siRNA-ionizable LNPs had a longer shelf life at 4°C. Our thermocycling technology showed an effective alternative to microfluidics technology in the production of nucleic acid-ionizable LNPs to meet global demand. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10717544
- Volume :
- 29
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Drug Delivery
- Publication Type :
- Academic Journal
- Accession number :
- 161644079
- Full Text :
- https://doi.org/10.1080/10717544.2022.2108523