title: Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer.
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.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Keisei
authors.initials: K
authors.lastname: Aki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Harasawa
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D000838:Anions; D050091:Dendrimers / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D005822:Genetic Vectors; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D010316:Particle Size; D004364:Pharmaceutical Preparations; D011108:Polymers / Q000737:chemistry*
chemical_list: D000838:Anions; D050091:Dendrimers; C104700:PAMAM Starburst; D004364:Pharmaceutical Preparations; D011108:Polymers