Tuning Macromolecular Structures of Synthetic Vectors for Gene Therapy
Résumé
The synthesis of triblocks poly(2‐methyl‐2‐oxazoline‐b‐tetrahydrofurane‐b‐2‐methyl‐2‐oxazoline) has been developed. It was shown that the technique of polymerization of the second block from the living species created on the two chain ends of poly(THF) is successful but makes the control of the size of the poly(THF) block difficult due a fast depolymerization upon the introduction of the second monomer. A purification technique was used to get rid of the possible homopoly(2‐methyl‐2‐oxazoline) formed. Various analytical techniques were used to characterize the behavior of the triblock and more particularly in the presence of DNA. Electrophoresis on agarose gels and neutron scattering, demonstrated that the neutral triblock does not appreciably interact with DNA. It was also shown that the triblock for which approximately half (47%) of the methyloxazoline units were transformed into ethylenimine units by hydrolysis gives only loose interactions with DNA. This result is assigned to the fact that charge density plays a major role in the interactions of positive polyelectrolytes with the negatively charged DNA. The triblock was shown being able to interact with bilayer lipid membranes mimicking cell membranes. The efficiency of the hydrolysed triblock was much higher, while the size of holes created in the membranes is not large enough to give passage to DNA.