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Amphiphilic Poly[(propylene glycol)‐ block ‐(2‐methyl‐2‐oxazoline)] Copolymers for Gene Transfer in Skeletal Muscle
Author(s) -
Brissault Blandine,
Kichler Antoine,
Leborgne Christian,
Jarroux Nathalie,
Cheradame Hervé,
Guis Christine
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700068
Subject(s) - amphiphile , ethylene glycol , copolymer , peg ratio , transfection , polymer chemistry , moiety , polyvinyl alcohol , poloxamer , chemistry , materials science , polymer , biophysics , organic chemistry , biochemistry , gene , finance , biology , economics
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.