title: Amphoteric agmatine containing polyamidoamines as carriers for plasmid DNA in vitro and in vivo delivery.
abstract: In this paper we report on the investigation, as DNA nonviral carriers, of three samples of an amphoteric polyamidoamine bearing 4-aminobutylguanidine deriving units, AGMA5, AGMA10, and AGMA20, characterized by different molecular weights (M(w) 5100, 10100, and 20500, respectively). All samples condensed DNA in spherical, positively charged nanoparticles and protected it against enzymatic degradation. AGMA10 and AGMA20 polyplexes had average diameters lower than 100 nm. AGMA5 polyplexes were larger. All polyplexes showed negligible cytotoxicity and were internalized in cells. AGMA10 and AGMA20 performed differently from AGMA5 as nucleic acid carriers in vitro. AGMA10 and AGMA20 effectively promoted transfection, whereas AGMA5 was ineffective. FITC-labeled AGMA10 was prepared and the intracellular trafficking of its DNA polyplex was studied. DNA/AGMA10 polyplex was largely localized inside the nucleus, while AGMA10 concentrated in the perinuclear region. DNA/AGMA10 polyplex intravenously administered to mice promoted gene expression in liver but not in other organs without detectable toxic side effects.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.forename: Agnese
authors.initials: A
authors.lastname: Bisazza
authors.forename: Roberto
authors.initials: R
authors.lastname: Sessa
authors.forename: Luca
authors.initials: L
authors.lastname: Primo
authors.forename: Fabio
authors.initials: F
authors.lastname: Fenili
authors.forename: Amedea
authors.initials: A
authors.lastname: Manfredi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ranucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferruti
mesh_terms: D000376:Agmatine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D003851:Deoxyribonucleases / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011073:Polyamines / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D014162:Transfection
chemical_list: C521880:AGMA1 polymer; D004337:Drug Carriers; D011073:Polyamines; D000376:Agmatine; D004247:DNA; D003851:Deoxyribonucleases