Optimization of Lipid Nanoformulations for Effective MRNA Delivery

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2022 Jul 11

PMID 35814615

Authors

Huiling Chen

Xuan Ren

Shi Xu

Dekui Zhang

Tiyun Han

Affiliations

Soon will be listed here.

Abstract

Introduction: Since the coronavirus disease 2019 (COVID-19) pandemic, the value of mRNA vaccine has been widely recognized worldwide. Messenger RNA (mRNA) therapy platform provides a promising alternative to DNA delivery in non-viral gene therapy. Lipid nanoparticles (LNPs), as effective mRNA delivery carriers, have been highly valued by the pharmaceutical industry, and many LNPs have entered clinical trials.

Methods: We developed an ideal lipid nanoformulation, named LNP3, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and cholesterol, and observed its release efficiency, sustained release, organ specific targeting and thermal stability.

Results: In vitro studies showed that the transfection efficiency of LNP3 was higher than that of LNPs composed of DOTAP-DOPE and DOTAP-cholesterol. The positive to negative charge ratio of LNPs is a determinant of mRNA transfer efficiency in different cell lines. We noted that the buffer affected the packaging of mRNA LNPs and identified sodium potassium magnesium calcium and glucose solution (SPMCG) as a favorable buffer formulation. LNP3 suspension can be lyophilized into a thermally stable formulation to maintain activity after rehydration both in vitro and in vivo. Finally, LNP3 showed sustained release and organ specific targeting.

Conclusion: We have developed an ideal lipid nanoformulation composed of DOTAP, DOPE and cholesterol for effective mRNA delivery.

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