Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer |
| |
Authors: | Kurosaki Tomoaki Yamashita Yumi Aki Keisei Harasawa Hitomi Nakagawa Hiroo Kodama Yukinobu Higuchi Norihide Nakamura Tadahiro Kitahara Takashi Sasaki Hitoshi |
| |
Institution: | Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki 852-8501, Japan. |
| |
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 γ-polyglutamic acid (γ-PGA)/PAMAM dendriplex and the α-PGA/PAMAM dendriplex formed a stable complex, although α-polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the ζ-potential, 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 γ-PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the α-PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the γ-PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The γ-PGA/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 γ-PGA 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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|