Cited by 71RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

siRNA-lipid nanoparticles with long-term storage stability facilitate potent gene-silencing in vivo

Suzuki, Y., Hyodo, K., Tanaka, Y., Ishihara, H.·2015·Journal of Controlled Release

Abstract

Considerable efforts have been directed towards discovering and developing delivery vehicles for RNA therapeutics. While most studies emphasize the efficacy and safety of these delivery vehicles, few reports conduct a comprehensive assessment of their storage stability, a critical property for practical applications. Here, we report a potent and safe lipid nanoparticle with long-term storage stability. Through chemical synthesis and screening of cationic lipids, a formulation has been identified that enables potent knockdown of hepatocyte proteins in mice upon intravenous administration (siRNA ED50 ~0.02 mg/kg). Toxicity studies revealed that a dose of 2mg/kg was well tolerated in rats, the most sensitive rodent model. We identified that a cyclic chemical structure in cationic lipids improved particle stability. The nanoparticles showed over 1.5 year storage stability as a liquid, with over 90% siRNA encapsulation without any changes in particle size. This novel delivery material has promising potential as a drug product that could bring RNA therapeutics to the treatment of liver-related disorders.

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Registry

Crossref · 10.1016/j.jconrel.2015.10.024

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41 of 41 references verified0 citation errors · 0 not checkable

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  • siRNA-LNPs are stable over 1.5 years at 4 °C.

    “Complementary research by Suzuki et al. showed that siRNA-LNPs are stable over the experimental period, i.e. 1.5 years, at 4 °C (Suzuki et al., 2015).”

    From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Suzuki et al., 2015

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Authors
Suzuki, Y., Hyodo, K., Tanaka, Y., & Ishihara, H.
Affiliations
  • Eisai (Japan) (JP)
  • SOGO Pharmaceutical Co., Ltd. (Japan) (JP)
Corresponding author
Suzuki, Y.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2015-12
Volume
220
Issue
Pt A
Pages
44-50
ISSN
0168-3659 (ISSN-L)
OpenAlex
W2114387194
Cited by
71
References
41
Citations by year
2026: 8 · 2025: 7 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 1 · 2017: 4 · 2016: 7
FWCI
1.74
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords
storage stability, cationic lipids, gene silencing, intravenous administration, nanoparticle toxicity, siRNA encapsulation, liver disease
MeSH terms
Animals, Lipids, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Time Factors, Gene Silencing, RNA, Small Interfering, Mice, Nanoparticles

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