Amphiphilic poly[(propylene glycol)-block-(2-methyl-2-oxazoline)] copolymers for gene transfer in skeletal muscle.
Amphiphilic triblock copolymers such as poly(ethylene glycol-b-propylene glycol-b-ethylene glycol) PE6400 (PEG(13)-PPG(30)-PEG(13)) have been recently shown to promote gene transfer in muscle. Herein we investigated the effect of a chemical change of the PEG moiety on the transfection activity of these compounds. We synthesized new amphiphilic copolymers in which the PEG end blocks are replaced by more hydrophilic poly(2-methyl-2-oxazoline) (PMeOxz) chains of various lengths. The resulting triblock PMeOxz-PPG-PMeOxz compounds were characterized by NMR, SEC, TGA, and DSC techniques and assayed for in vivo muscle gene transfer. The results confirm both the block structure and the monomer unit composition (DP(PG)/DP(MeOxz)) of the new PPG(34)-PMeOxz(41) and PPG(34)-PMeOxz(21) triblock copolymers. Furthermore, in vivo experiments show that these copolymers are able to significantly increase DNA transfection efficiency, despite the fact that their chemical nature and hydrophilic character are different from the poloxamers. Overall, these results show that the capacity to enhance DNA transfection in skeletal muscle is not restricted to PEG-PPG-PEG arrangements.
Brissault
Blandine
B
Laboratoire Matériaux Polymères aux Interfaces-UMR CNRS 7581, Université d'Evry, 91025 Evry, France.
Kichler
Antoine
A
Leborgne
Christian
C
Jarroux
Nathalie
N
Cheradame
Hervé
H
Guis
Christine
C
D000818:Animals; D002460:Cell Line; D005650:Fumarates; D018014:Gene Transfer Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates; D018482:Muscle, Skeletal / Q000378:metabolism*; D010080:Oxazoles / Q000737:chemistry*; D011126:Polypropylenes
D005650:Fumarates; D008689:Methacrylates; D010080:Oxazoles; C446719:Polypropylene fumarate-phloroglucinol triglycidyl methacrylate; D011126:Polypropylenes