Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes.

Abstract:

:We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-L-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol). The ternary complexes were constructed by the addition of γ-polyglutamic acid (γ-PGA) to the binary complexes. The complexes were approximately 54-153 nm in particle size. The binary complexes showed a cationic surface charge although an anionic surface charge was observed in the ternary complexes. The polymer-based complexes did not show a silencing effect in the mouse colon carcinoma cell line expressing luciferase regularly (Colon26/Luc cells). The binary complexes based on liposomes and their ternary complexes coated by γ-PGA showed a significant silencing effect. The binary complexes showed significant cytotoxicity although the ternary complexes coated by γ-PGA did not show significant cytotoxicity. The ternary complexes coated by γ-PGA suppressed luciferase activity in the tumor after their direct injection into the tumors of mice bearing Colon26/Luc cells. Thus, we have newly identified safe and efficient ternary complexes of siRNA for clinical use.

journal_name

Biol Pharm Bull

authors

Kodama Y,Harauchi S,Kawanabe S,Ichikawa N,Nakagawa H,Muro T,Higuchi N,Nakamura T,Kitahara T,Sasaki H

doi

10.1248/bpb.b13-00054

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

995-1001

issue

6

eissn

0918-6158

issn

1347-5215

pii

DN/JST.JSTAGE/bpb/b13-00054

journal_volume

36

pub_type

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