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Updated: Jun 14, 2026
Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
Liposomal lipid nanoparticles containing dihydrosphingomyelin exhibit improved stability and extended hepatic and
Suiyang Liao1, Kevin Fox2, Alexandra Birkenshaw3
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver V6T 1Z3, Canada; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Lipid nanoparticles (LNP) are currently the most advanced delivery platform for mRNA therapeutics. To reach extrahepatic tissues, it is beneficial to engineer LNP-mRNA systems with improved stability and prolonged blood circulation lifetimes. In previous work we have shown that LNP-mRNA systems with liposomal morphology that contain egg sphingomyelin (ESM) can exhibit longer circulation lifetimes and improved extrahepatic delivery. Here we extend this work to investigate the effects of employing dihydrosphingomyelin (DHSM) as the helper lipid on liposomal LNP performance. We show that inclusion of DHSM substantially extends the blood circulation half-life, thus improving the extrahepatic distribution of LNPs. Further, the presence of DHSM leads to a substantial improvement in transfection of hepatic and extra-hepatic tissues as compared to liposomal LNP systems containing ESM.
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