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Impact of Non-ionizable Lipids and Phase Mixing Methods on Structural Properties of Lipid Nanoparticle Formulations by Anna Pratsinis; Yuchen Fan; Michaela Portmann; Michal Hammel; Ponien Kou; Apoorva Sarode; Philippe Ringler; Lubomir Kovacik; Matthias E. Lauer; Jens Lamerz; Greg L. Hura; Chun-Wan Yen; Michael Keller is a Pharmacology, Toxicology and Pharmaceutics article available to read on EtoBox.
What is Impact of Non-ionizable Lipids and Phase Mixing Methods on Structural Properties of Lipid Nanoparticle Formulations about?
Lipid nanoparticles (LNPs) have been widely investigated for nucleic acid therapeutic delivery, and demonstrated their potential in enabling new mRNA vaccines. LNPs are usually formulated with multi-lipid components and the composition variables may impact their structural properties. Here, we investigated the impact of helper lipids on physicochemical properties of LNPs using a Design of Experiments (DoE) definitive screening design. Phospholipid head group, degree of unsaturation, ratio to cholesterol as well as PEG-lipid content were varied and a series of 14 LNPs were prepared by microfluidic- and solvent-injection mixing. Solvent-injection mixing by a robotic liquid handler yielded 50–225 nm nanoparticles with highly ordered, ∼5 nm inter-lamellar spacing as measured by small angle X-ray scattering (SAXS) and confirmed by cryo-transmission electron microscopy (cryo-EM). In contrast, microfluidic mixing resulted in less ordered, notably smaller (50–75 nm) and more homogenous nanoparticles. Significant impacts of the stealth-lipid DSPE-PEG2000 on nanoparticle size, polydispersity and encapsulation efficiency of an oligonucleotide cargo were observed in LNPs produced by both metho
Who reads Impact of Non-ionizable Lipids and Phase Mixing Methods on Structural Properties of Lipid Nanoparticle Formulations?
It is typically read by researchers, students, and practitioners in Pharmacology, Toxicology and Pharmaceutics.
- Author
- Anna Pratsinis; Yuchen Fan; Michaela Portmann; Michal Hammel; Ponien Kou; Apoorva Sarode; Philippe Ringler; Lubomir Kovacik; Matthias E. Lauer; Jens Lamerz; Greg L. Hura; Chun-Wan Yen; Michael Keller
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Pharmacology, Toxicology and Pharmaceutics (Life Sciences)