Localization of Intramuscular mRNA Delivery Using Deep Eutectic‐Lipid Nanocomposites

Author:

Curreri Alexander Michael12,Dunne Michael12,Bibbey Michael Griffith12,Kapate Neha123,Kim Jayoung14,Mitragotri Samir12ORCID

Affiliation:

1. John A. Paulson School of Engineering and Applied Sciences Harvard University 150 Western Ave Allston MA 02134 USA

2. Wyss Institute for Biologically Inspired Engineering at Harvard University 3 Blackfan St Boston MA 02115 USA

3. Harvard‐MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA 02139 USA

4. Department of Pharmaceutical Sciences College of Pharmacy University of North Texas Health Science Center at Forth Worth 3500 Camp Bowie Blvd. Forth Worth TX 76107 USA

Abstract

AbstractMessenger ribonucleic acid (mRNA) has long been touted as a next‐generation therapeutic modality for infectious disease, cancer, and genetic disorders. Lipid nanoparticles (LNPs) provide an elegant delivery strategy for mRNA cargo to help realize this potential for vaccination. However, systemic exposure seen with traditional LNP formulations can have significant implications on efficacy and safety. Efforts to mitigate this have largely been focused on laborious lipid or LNP redesign. Here, the use of a deep eutectic‐lipid nanocomposite delivery system for the tuning of mRNA expression for intramuscular injections in vivo is reported. One deep eutectic, cholinium malonate, allows for the linear control of percent expression at the muscular injection site based solely on its concentration in the formulation. The same deep eutectic solvent (DES) can increase local muscle expression by 68% and significantly decrease off‐target liver expression by 72%. Physico‐chemical studies suggest that the DES incorporates into or onto the pre‐formed LNPs thus impacting endosomal escape and in situ interactions. These nanocomposites provide new possibilities for previously approved LNP formulations and without the need for lipid redesign to induce localized expression.

Publisher

Wiley

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