2. Academic Validation
  3. Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice

Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice

  • Int J Pharm. 2023 Mar 25;122896. doi: 10.1016/j.ijpharm.2023.122896.
Longjian Geng 1,  Naoya Kato 2,  Yukinobu Kodama 3,  Hidefumi Mukai 4,  Shigeru Kawakami 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: bb55319951@ms.nagasaki-u.ac.jp.
  • 2 Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: bb55319401@ms.nagasaki-u.ac.jp.
  • 3 Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8501, Japan. Electronic address: y-kodama@nagasaki-u.ac.jp.
  • 4 Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan; Laboratory for Molecular Delivery and Imaging Technology, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: hmukai@nagasaki-u.ac.jp.
  • 5 Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: skawakam@nagasaki-u.ac.jp.
PMID: 36972778 DOI: 10.1016/j.ijpharm.2023.122896
Abstract

Intratracheal (i.t.) administration, which takes advantage of the specific structure of the respiratory system, can effectively deliver nanoparticles to the lung. Much remains unknown about the i.t. administration of messenger RNA (mRNA)-lipid nanoparticles (LNPs) and the effect of lipid composition. In this study, we administered minute amounts of mRNA-LNP solutions into mice intratracheally and investigated the effect of lipid composition on protein expression in the lungs. We first validated higher protein expression with mRNA-LNP compared to that with mRNA-PEI complex and naked mRNA. Then, we evaluated the influence of lipid composition of LNPs on the protein expression and found that: 1) decreasing the PEG molarity from 1.5% to 0.5% could significantly increase the protein expression; 2) replacing DMG-PEG with DSG-PEG could slightly increase the protein expression; 3) using DOPE instead of DSPC could increase protein expression by an order of magnitude. We successfully prepared an mRNA-LNP with optimal lipid compositions that led to robust protein expression following i.t. administration, thus providing meaningful insights into advanced development of mRNA-LNPs for therapeutic i.t. administration.

Keywords

Intratracheal administration; Lipid composition; Lipid nanoparticle; Lung; Protein expression.

Figures
Products