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Hydrophilic and hydrophobic copolymers of a polyasparthylhydrazide bearing positive charges as vector for gene therapy

  • Autori: Cavallaro, G.; Licciardi, M.; Mandracchia, D.; Pitarresi, G.; Giammona, G.
  • Anno di pubblicazione: 2008
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: polyion complex; cationic polyaminoacids; DNA protection; PAHy-GTA copolymers, polyaspartylhydrazide
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Background: The design of polymeric vectors for gene delivery provided with specific properties is one of the most critical aspects for a successful gene therapy. These polymers should be biocompatible as well as able to carry efficiently DNA to target tissues and to transfect it into cells. Results: The formation of complexes of poly[(α,β-asparthylhydrazide)-poly(ethylene glycol)] and poly[(α,β-asparthylhydrazide)-hexadecylamine] copolymers functionalised with glycidyltrimethylammonium chloride (PAHy-PEG-GTA and PAHy-C16-GTA, respectively) with DNA was studied. The effects of the introduction of hydrophilic (PEG) or hydrophobic (C16) moieties on the chains of PAHy-GTA copolymers, such as the stabilising effect on the DNA structure, were evaluated. In particular, we observed a high DNA protection by PAHy-PEG-GTA copolymers. Degradation studies led us to suppose a particular aqueous conformation of the polyionic complex of PAHy-PEG2000-GTA in which DNA should be internalised into an inner core surrounded by a PEG hydrophilic shell; while no significant protection was detected with PAHy-C16-GTA in which DNA should be disposed on the surface of the complex, freely exposed to DNase II action. Conclusion: The insertion of PEG or C16 chains into the polymeric structure of PAHy-GTA copolymers changes significantly the DNA complexing and protecting ability of the PAHy-GTA copolymers, showing that hydrophilic and hydrophobic side chains can play a crucial role in supramolecular arrangements of interpolyelectrolyte complexes between DNA and PAHy copolymers.