title: Efficient Packaging of Plasmid DNA Using a pH Sensitive Cationic Lipid for Delivery to Hepatocytes.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hada
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D002412:Cations / Q000627:therapeutic use; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004349:Drug Packaging; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D022781:Hepatocytes; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D008081:Liposomes; D008099:Liver / Q000166:cytology*; D008156:Luciferases; D008297:Male; D008813:Mice, Inbred ICR; D053769:Nanocapsules; D009696:Nucleic Acids / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage* / Q000627:therapeutic use; D010957:Plasmids; D034741:RNA, Small Interfering
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D053769:Nanocapsules; D009696:Nucleic Acids; D010880:Piperidines; D034741:RNA, Small Interfering; C580570:YSK05; D004247:DNA; D008156:Luciferases