Efficient packaging of plasmid DNA using a pH sensitive cationic lipid for delivery to hepatocytes

Yu Sakurai, Takashi Matsuda, Tomoya Hada, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Plasmid DNA (pDNA) is expected to be a new class of medicine for treating currently incurable diseases. To deliver these nucleic acids, we developed a liposomal delivery system we have called a multifunctional envelope-type nano device (MEND). In this report, we demonstrate that a MEND containing a pH-sensitive cationic lipid, YSK05 (YSK-MEND), efficiently delivered pDNA via systemic injection, and that its expression was highly dependent on the encapsulation state of the pDNA. In the preparation, the pH, ionic strength, and sodium chloride (NaCl) concentration of the lipid/pDNA mixture strongly affected the encapsulation efficiency of pDNA. Additionally, the transgene expression of luciferase in the liver by the injected YSK-MEND was dependent on the encapsulation state of pDNA rather than the nature of the YSK-MEND. Confocal laser scanning microscopy findings revealed that injection of the YSK-MEND led to homogenous gene expression in the liver compared to injection via the hydrodynamic tail vein (HTV). Concerning the safety of the YSK-MEND, a transient increase in the activity of liver enzymes was observed. However, no significant adverse events were observed. Taken together, the YSK-MEND represents a potentially attractive therapy for the treatment of various hepatic diseases.

Original languageEnglish
Pages (from-to)1185-1191
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume38
Issue number8
DOIs
Publication statusPublished - 2015 Aug 1
Externally publishedYes

Keywords

  • Hepatic delivery
  • Liposome
  • PH-sensitive lipid
  • Plasmid DNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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