Safe and Effective Delivery of Small Interfering RNA with Polymer- and Liposomes-Based Complexes
-
- Kodama Yukinobu
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Harauchi Satoe
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Kawanabe Saki
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Ichikawa Nobuhiro
- College of Pharmaceutical Sciences, Ritsumeikan University
-
- Nakagawa Hiroo
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Muro Takahiro
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Higuchi Norihide
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Nakamura Tadahiro
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Kitahara Takashi
- Department of Hospital Pharmacy, Nagasaki University Hospital
-
- Sasaki Hitoshi
- Department of Hospital Pharmacy, Nagasaki University Hospital Global COE Program, Nagasaki University
Search this article
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
-
- Biological and Pharmaceutical Bulletin
-
Biological and Pharmaceutical Bulletin 36 (6), 995-1001, 2013
The Pharmaceutical Society of Japan
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1390282679608106496
-
- NII Article ID
- 130003361445
-
- NII Book ID
- AA10885497
-
- COI
- 1:STN:280:DC%2BC3snovFSjsQ%3D%3D
-
- ISSN
- 13475215
- 09186158
-
- HANDLE
- 10069/33126
-
- NDL BIB ID
- 024524403
-
- PubMed
- 23727920
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- IRDB
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
-
- Abstract License Flag
- Disallowed