Long-term storage of lipid-like nanoparticles for mRNA delivery

Pengxuan Zhao; Xucheng Hou; Jingyue Yan; Shi Du; Yonger Xue; Wenqing Li; Guangya Xiang; Yizhou Dong

doi:10.1016/j.bioactmat.2020.03.001

Long-term storage of lipid-like nanoparticles for mRNA delivery

Bioact Mater. 2020 Mar 18;5(2):358-363. doi: 10.1016/j.bioactmat.2020.03.001. eCollection 2020 Jun.

Authors

Pengxuan Zhao^{1

2}, Xucheng Hou¹, Jingyue Yan¹, Shi Du¹, Yonger Xue¹, Wenqing Li¹, Guangya Xiang², Yizhou Dong^{1

3

4

5

6

7}

Affiliations

¹ Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, United States.
² School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
³ Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, United States.
⁴ The Center for Clinical and Translational Science, The Ohio State University, Columbus, OH, 43210, United States.
⁵ The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, United States.
⁶ Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, 43210, United States.
⁷ Department of Radiation Oncology, The Ohio State University, Columbus, OH, 43210, United States.

Abstract

Lipid-like nanoparticles (LLNs) have been extensively explored for messenger RNA (mRNA) delivery in various biomedical applications. However, the long-term storage of these nanoparticles is still a challenge for their clinical translation. In this study, we investigated a series of conditions for the long-term storage of LLNs with encapsulation of mRNA. We evaluated the stability of LLNs with different concentrations of cryoprotectants (sucrose, trehalose or mannitol) under the conditions of freezing or lyophilization processes. Through in vitro and in vivo mRNA delivery studies, we identified the optimal storage condition, and found that the addition with 5% (w/v) sucrose or trehalose to LLNs could remain their mRNA delivery efficiency for at least three months in the liquid nitrogen storage condition.

Keywords: Lipid-like nanoparticles; Long-term storage; mRNA delivery.