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Published on: February 1, 2019
Diethylene glycol monoethyl ether as an alternative solvent for mRNA-LNP manufacture
Catherine Ross1, Sarah Lindsay1, Sara Barham1
1Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral St, University of Strathclyde, Glasgow, G4 0RE, United Kingdom.
Objectives:
To evaluate diethylene glycol monoethyl ether (DEGEE) as an alternative organic solvent to ethanol for mRNA lipid nanoparticle (LNP) manufacture.
Methods:
LNPs composed of distearoyl phosphatidylcholine, cholesterol, a PEGylated lipid and one of four ionizable lipids (SM-102, ALC-0315, Dlin-MC3-DMA or C12-200) were prepared using ethanol or DEGEE. Physicochemical properties were characterized using dynamic light scattering, nanoparticle tracking analysis, single-particle Raman analysis, and asymmetric flow field-flow fractionation. Gas chromatography confirmed solvent removal following purification. Membrane-disruptive activity was evaluated under physiological and endosomal-like pH conditions, and in vivo protein expression was used to assess functional mRNA delivery.
Key Findings:
Across the four LNP formulations tested, DEGEE supported the production of LNPs with physicochemical and biological performance equivalent to ethanol-manufactured LNPs. Both solvents were effectively removed using standard purification workflows, and particle size, polydispersity, zeta potential, encapsulation efficiency, and pH-responsive membrane-disruptive activity were not affected by solvent substitution. In vivo studies further demonstrated comparable protein expression profiles for DEGEE- and ethanol-manufactured LNPs.
Conclusions:
DEGEE is a viable alternative to ethanol for mRNA-LNP manufacture, expanding the solvent options available for formulation development and scalable LNP production.
