Elucidation of the physicochemical properties and potency of siRNA-loaded small-sized lipid nanoparticles for siRNA delivery

Yusuke Sato, Yusuke Note, Masatoshi Maeki, Noritada Kaji, Yoshinobu Baba, Manabu Tokeshi, Hideyoshi Harashima

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Because nanoparticles with diameters less than 50 nm penetrate stromal-rich tumor tissues more efficiently, the synthesis of small-sized nanoparticles encapsulating short interfering RNA (siRNA) is important in terms of realizing novel siRNA medicine for the treatment of various cancers. Lipid nanoparticles (LNPs) are the leading systems for the delivery of siRNA in vivo. Limit size LNPs were successfully synthesized using a microfluidic mixing technique. However, the physicochemical properties and potential for in vivo siRNA delivery of the limit-size LNPs have not been examined in detail. In the present study, we prepared LNPs with different diameters from 32 to 67 nm using a microfluidic mixing devise and examined the physicochemical properties of the particles and the potential for their use in delivering siRNA in vitro and in vivo to liver. Reducing the size of the LNPs causes poor-packing and an increased surface area, which result in their instability in serum. Moreover, it was revealed that the ability of endosomal escape (cytosolic siRNA release) of the smaller LNPs is subject to inhibition by serum compared to that of larger counterparts. Taken together, an increase in packing and avoiding the adsorption of serum components are key strategies for the development of next-generation highly potent and small-sized LNPs.

Original languageEnglish
Pages (from-to)48-57
Number of pages10
JournalJournal of Controlled Release
Volume229
DOIs
Publication statusPublished - May 10 2016
Externally publishedYes

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Nanoparticles
Small Interfering RNA
Lipids
Microfluidics
Serum
Adsorption
Neoplasms
Liver

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Elucidation of the physicochemical properties and potency of siRNA-loaded small-sized lipid nanoparticles for siRNA delivery. / Sato, Yusuke; Note, Yusuke; Maeki, Masatoshi; Kaji, Noritada; Baba, Yoshinobu; Tokeshi, Manabu; Harashima, Hideyoshi.

In: Journal of Controlled Release, Vol. 229, 10.05.2016, p. 48-57.

Research output: Contribution to journalArticle

Sato, Yusuke ; Note, Yusuke ; Maeki, Masatoshi ; Kaji, Noritada ; Baba, Yoshinobu ; Tokeshi, Manabu ; Harashima, Hideyoshi. / Elucidation of the physicochemical properties and potency of siRNA-loaded small-sized lipid nanoparticles for siRNA delivery. In: Journal of Controlled Release. 2016 ; Vol. 229. pp. 48-57.
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