Synthesis, characterization, and gene transfer application of poly(ethylene glycol-b-ethylenimine) with high molar mass polyamine block.
The study of ethyloxazoline/methyloxazoline (EtOXZ/MeOXZ) copolymerization, initiated by methyl tosylate (MeOTs), showed that (i) incorporation of MeOXZ units into random copolymer becomes effective over DP = 100 and (ii) propagation process proceeds with negligible transfer to monomer up to a DP of 400 despite the presence of MeOXZ in the polymerization medium. These results produced random poly(EtOXZ-co-MeOXZ) copolymers with various molar composition ratios in alkyloxazoline units. The close values found for the comonomer reactivity ratios in acetonitrile (r(1MeOXZ) = 1.18; r(2EtOXZ) = 0.34) implied a random chain organization in short sequences of each repeating unit, which was an important parameter in view of the optimization of their subsequent modification: the alkaline hydrolysis was successfully achieved when the MeOXZ unit content of the polyoxazoline chains reached 75%. Using these results, the diblock copolymer poly(ethylene glycol-b-(ethyloxazoline-co-methyloxazoline)) (poly(EG-b-(EtOXZ-co-MeOXZ))) with high DP was synthesized by cationic copolymerization of EtOXZ/MeOXZ comonomers using CH(3)-PEG(2kDa)-Ts as macroinitiator. The comonomer composition of this new compound was adjusted in order to optimize the hydrolysis step and obtain finally the diblock copolymer poly(ethylene glycol-b-ethylenimine) (poly(EG-b-EI)). The high molar mass of this copolymer was confirmed both by (1)H NMR and SANS measurements. Gene delivery experiments showed that the copolymer has significant DNA transfection capacities.
Brissault
B
B
Laboratoire Matériaux Polymères aux Interfaces, UMR CNRS 7581, Université d'Evry, 91025 Evry Cedex, France.
Kichler
A
A
Leborgne
C
C
Danos
O
O
Cheradame
H
H
Gau
J
J
Auvray
L
L
Guis
C
C
D001672:Biocompatible Materials / Q000737:chemistry*; D002412:Cations; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D006868:Hydrolysis; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D014162:Transfection
D001672:Biocompatible Materials; D002412:Cations; D011073:Polyamines; D011108:Polymers; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA