Secure and Effective Gene Vector of Polyamidoamine Dendrimer Pharmaceutically Modified with Anionic Polymer

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 gamma-polyglutamic acid (gamma-PGA)/PAMAM dendriplex and the alpha-PGA/PAMAM dendriplex formed a stable complex, although alpha-polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the zeta-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 gamma-PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the alpha-PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the gamma-PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The gamma-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 gamma-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. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 4855-4863, 2011