Enhanced stability of siRNA-loaded lipid nanoparticles during lyophilization via acetyl-arginine and disaccharides
5 affiliations
- 1College of Pharmacy, Mokpo National University, Muan, 58554, Republic of Korea
- 2Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Muan, 58554, Republic of Korea
- 3College of Pharmacy, Dongguk University, Gyeonggi, 10326, Republic of Korea
- 4Enhanced Bio Inc. R&D Center, Seoul, 04779, Republic of Korea
- 5College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea
Abstract
RNA-loaded lipid nanoparticles (LNPs) are highly sensitive to temperature fluctuations, which present significant challenges for storage and transportation. Lyophilization is a potential strategy to enhance storage stability; however, the freeze-drying process can subject nanoparticles to stresses that may alter their physicochemical properties and compromise RNA integrity. This study evaluated the effects of formulation composition on the stability and functionality of small interfering RNA (siRNA)-loaded LNPs after lyophilization. Among the formulations tested, a combination of 10% (w/v) trehalose and 50 mM N-acetyl-L-arginine (NALA) most effectively preserved particle size and encapsulation efficiency following freeze-drying. The NALA-based formulation also exhibited improved storage stability across 4 °C, 25 °C, and 40 °C compared to the corresponding arginine-containing formulation. Cryo-TEM analysis revealed that NALA-containing LNPs retained a spherical morphology with a homogeneous internal core after lyophilization, indicating improved structural preservation during freeze-drying. Additionally, reconstituted siRNA-LNPs containing NALA maintained cellular function comparable to pre-lyophilization samples. These findings demonstrate that a stabilizer system based on trehalose and NALA can enhance the stability of lyophilized siRNA-LNPs while preserving their physicochemical properties and biological activity.
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BibTeX
@article{kim2026enhanced,
title = {{Enhanced stability of siRNA-loaded lipid nanoparticles during lyophilization via acetyl-arginine and disaccharides}},
author = {Ki Hyun Kim and Arun Mainali and Seung Hyun Pih and Hun Soon Jung and Hye Jeong Kim and Nam Ah Kim and Seong Hoon Jeong},
journal = {International Journal of Pharmaceutics: X},
year = {2026},
month = oct,
doi = {10.1016/j.ijpx.2026.100695},
url = {https://doi.org/10.1016/j.ijpx.2026.100695},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Enhanced stability of siRNA-loaded lipid nanoparticles during lyophilization via acetyl-arginine and disaccharides
AU - Ki Hyun Kim
AU - Arun Mainali
AU - Seung Hyun Pih
AU - Hun Soon Jung
AU - Hye Jeong Kim
AU - Nam Ah Kim
AU - Seong Hoon Jeong
PY - 2026
DA - 2026/10/24
JO - International Journal of Pharmaceutics: X
DO - 10.1016/j.ijpx.2026.100695
UR - https://doi.org/10.1016/j.ijpx.2026.100695
AB - RNA-loaded lipid nanoparticles (LNPs) are highly sensitive to temperature fluctuations, which present significant challenges for storage and transportation. Lyophilization is a potential strategy to enhance storage stability; however, the freeze-drying process can subject nanoparticles to stresses that may alter their physicochemical properties and compromise RNA integrity. This study evaluated the effects of formulation composition on the stability and functionality of small interfering RNA (siRNA)-loaded LNPs after lyophilization. Among the formulations tested, a combination of 10% (w/v) trehalose and 50 mM N-acetyl-L-arginine (NALA) most effectively preserved particle size and encapsulation efficiency following freeze-drying. The NALA-based formulation also exhibited improved storage stability across 4 °C, 25 °C, and 40 °C compared to the corresponding arginine-containing formulation. Cryo-TEM analysis revealed that NALA-containing LNPs retained a spherical morphology with a homogeneous internal core after lyophilization, indicating improved structural preservation during freeze-drying. Additionally, reconstituted siRNA-LNPs containing NALA maintained cellular function comparable to pre-lyophilization samples. These findings demonstrate that a stabilizer system based on trehalose and NALA can enhance the stability of lyophilized siRNA-LNPs while preserving their physicochemical properties and biological activity.
SN - 2590-1567
ER -