Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486185 | Journal of Pharmaceutical Sciences | 2011 | 9 Pages |
Abstract
The purpose of this study was to develop a new type of gene vector, polyamidoamine (PAMAM) dendriplex pharmaceutically modified, based on electrostatic interactions, by various anionic polymers. The γâpolyglutamic acid (γâPGA)/PAMAM dendriplex and the αâPGA/PAMAM dendriplex formed a stable complex, although αâpolyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the ζâpotential, although it did not greatly affect the size of the complex. As a result of an in vitro gene expression study of mouse melanoma cells, we found that the γâPGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the αâPGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the γâPGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The γâPGA/PAMAM dendriplex showed no cytotoxicity and no agglutination, although severe cytotoxicity and agglutination were observed in the PAMAM dendriplex. Thus, we discovered that complexes of pDNA, PAMAM dendrimers, and γâPGA showed higher gene expression in vitro and in vivo, and markedly lower toxicity. This complex is valuable and is expected to be a safe and effective gene vector. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:4855-4863, 2011
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Tomoaki Kurosaki, Yumi Yamashita, Keisei Aki, Hitomi Harasawa, Hiroo Nakagawa, Yukinobu Kodama, Norihide Higuchi, Tadahiro Nakamura, Takashi Kitahara, Hitoshi Sasaki,