Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.

Abstract

The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.14). Compared to ordinary cationic liposomes (CLs), steric cationic liposomes (PEG-CLs) and 1% GA-PEG-CLs made from DOTAP/Chol/MPEG2000-Chol/GA-PEG-Chol at molar ratio of 50:45:4:1, 5% GA-PEG-CLs were found to possess the highest transfection efficiency as gene vectors in serum-free or serum-containing medium in PKCalpha over-expressed HepG2 cells but no significance difference in human embryonic kidney cell line HEK 293. Additionally, 5% GA-PEG-CLs have the lowest cytotoxicity on human normal hepatocyte cell line L02. The competitive inhibition experiments mediated by GA were carried out in HepG2 cells, which demonstrated that GA-PEG-CLs could deliver selectively pDNA to hepatoma cells by the targeting moiety GA. In conclusion, GA-PEG-CLs containing 5% GA-PEG-Chol might be one of the most potential gene vectors as hepatoma targeting therapy.

• Authors: Zhi Yao He, Xi Zheng, Xiao Hua Wu, Xiang Rong Song, Gu He, Wen Fang Wu, Shui Yu, Sheng Jun Mao, Yu Quan Wei
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 397 Issue 1-2 Pg. 147-54 (Sep 15 2010) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 20667672 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Cations
• Fatty Acids, Monounsaturated
• Liposomes
• Quaternary Ammonium Compounds
• poly(oxyethylene) cholesteryl ether
• Polyethylene Glycols
• Cholesterol
• 1,2-dioleoyloxy-3-(trimethylammonium)propane
• Glycyrrhetinic Acid

Topics

• Carcinoma, Hepatocellular (therapy)
• Cations
• Cholesterol (analogs & derivatives)
• Fatty Acids, Monounsaturated
• Genetic Therapy
• Genetic Vectors
• Glycyrrhetinic Acid
• HEK293 Cells
• Hep G2 Cells
• Humans
• Liposomes
• Liver Neoplasms (therapy)
• Particle Size
• Polyethylene Glycols
• Quaternary Ammonium Compounds
• Transfection