title: alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers (PAHy-GTA): novel polymers with potential for DNA delivery.
abstract: Hydrophilic polycations form complexes when mixed with plasmids. Following functionalisation with glycidyltrimethylammonium chloride (GTA) alpha,beta-poly(asparthylhydrazide) (PAHy), a water-soluble synthetic macromolecule, becomes polycationic and potentially useful for systemic gene delivery. Initially the biocompatibility of PAHy and PAHy-GTA derivatives with different degrees of positive charge substitution were studied and it was shown that PAHy-GTA was neither haemolytic nor cytotoxicity up to 1 mg/ml. After intravenous injection (125)I-labelled PAHy-GTA derivative containing 46 mol% (PAHy-GTA(b)) of trimethylammonium groups did not accumulate in the liver (4.1+/-0.9% of the recovered dose after 1 h) but was subjected to renal excretion (45+/-21% of the recovered dose was in the kidneys after 1 h). PAHy-GTA formed complexes with DNA (gel retardation) and they protected against degradation by DNase II. Finally the ability of the PAHy-GTA(b) derivative to mediate the transfection of HepG2 cells using the marker gene beta-galactosidase was studied. The optimum plasmid/polymer mass ratio was examined in comparison to LipofectACE, Lipofectin and polyethylenimine.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Universita' degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pedone
authors.forename: G
authors.initials: G
authors.lastname: Cavallaro
authors.forename: S C
authors.initials: SC
authors.lastname: Richardson
authors.forename: R
authors.initials: R
authors.lastname: Duncan
authors.forename: G
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D004706:Endodeoxyribonucleases / Q000494:pharmacology; D004852:Epoxy Compounds / Q000008:administration & dosage*; D015316:Genetic Therapy; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D010455:Peptides / Q000008:administration & dosage; D011108:Polymers; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004852:Epoxy Compounds; D010455:Peptides; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C442699:poly(aspartylhydrazide); C045006:glycidyl trimethylammonium; D004247:DNA; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II