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

Abstract

AbstractBACKGROUND: 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. Copyright © 2008 Society of Chemical Industry