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Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer

✍ Scribed by Tomoaki Kurosaki; Yumi Yamashita; Keisei Aki; Hitomi Harasawa; Hiroo Nakagawa; Yukinobu Kodama; Norihide Higuchi; Tadahiro Nakamura; Takashi Kitahara; Hitoshi Sasaki


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
342 KB
Volume
100
Category
Article
ISSN
0022-3549

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✦ Synopsis


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 (-polyglutamic acid ((-PGA)/PAMAM dendriplex and the "-PGA/PAMAM dendriplex formed a stable complex, although "-polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the .-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 (-PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the "-PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the (-PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The (-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, PA-MAM dendrimers, and (-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.


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