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- 조회447
Biomater. Res., 2024 May 22:28:0017 | https://doi.org/10.34133/bmr.0017
Development of Lipid Nanoparticle Formulation for the Repeated Administration of mRNA Therapeutics
Yeji Lee, Michaela Jeong, Gyeongseok Lee, Jeongeun Park, Hyein Jung,Seongeun Im, and Hyukjin Lee*
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul03760, Republic of Korea.
*Address correspondence to: Hyukjin Lee
Abstract
During the COVID-19 pandemic, mRNA vaccines emerged as a rapid and effective solution for global immunization. The success of COVID-19 mRNA vaccines has increased interest in the use of lipid nanoparticles (LNPs) for the in vivo delivery of mRNA therapeutics. Although mRNA exhibits robust expression profiles, transient protein expression is often observed, raising uncertainty regarding the frequency of its administration. Additionally, various RNA therapeutics may necessitate repeated dosing to achieve optimal therapeutic outcomes. Nevertheless, the impact of repeated administrations of mRNA/LNP on immune responses and protein expression efficacy remains unclear. In this study, we investigated the influence of the formulation parameters, specifically ionizable lipids and polyethylene glycol (PEG) lipids, on the repeat administration of mRNA/LNP. Our findings revealed that ionizable lipids had no discernible impact on the dose-responsive efficacy of repeat administrations, whereas the lipid structure and molar ratio of PEG lipids were primary factors that affected mRNA/LNP performance. The optimization of the LNP formulation with PEG lipid confirmed the sustained dose-responsive efficacy of mRNA after repeated administrations. This study highlights the critical importance of optimizing LNP formulations for mRNA therapeutics requiring repeated administrations.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-06-10)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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