Lipid nanoparticles under shear stress: mimicking the blood flow
Therapeutic treatments based on the protein production by delivering messenger RNA (mRNA) represent a promising approach. One of the major challenges is to protect mRNA from enzymatic degradation and deliver it into the target cells. Lipid nanoparticles (LNPs) formed by a cationic ionizable lipid (CIL), DSPC, cholesterol and a pegylated lipid were approved for delivery of small interference RNA. In vitro and in vivo studies often draw different conclusions when LNPs are involved and this may be due to the extremely different environments where the LNPs are immersed, not only in terms of molecular composition of the media but also due to responsiveness in the LNP to flow rate and shear. There is little known on the structural effects due to corona formation or due to the shear stress upon intravenous (IV) administration. Our recent results (currently being prepared for publication) suggest that Apolipoprotein E binding affects the LNP structure. We aim to characterize the LNP structure under shear stress comparable to blood flow both with and without the payload. In addition, we want to investigate if the ApoE binding to LNPs induces a change in the LNP response to shear stress.
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SEBASTIANI Federica; CARDENAS; PORCAR Lionel and Marianna Yanez Arteta. (2021). Lipid nanoparticles under shear stress: mimicking the blood flow. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-989
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