Synthesis and Evaluation of Amphiphilic Poly(tetrahydrofuran-b-ethylene oxide) Copolymers for DNA Delivery into Skeletal Muscle

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Abstract

Purpose

Amphiphilic triblock copolymers such as the pluronic poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) L64 (pEO13-pPO30-pEO13) have been shown to mediate more efficient gene transfer in muscle as compared to naked DNA. We were interested in studying the effect of a chemical change of the central block of pluronic polymers on the transfection activity.

Methods

We synthesized new amphiphilic copolymers in which the hydrophobic pPO block was replaced by poly(tetrahydrofuran) (pTHF) chains. The resulting triblock pEO–pTHF–pEO polymers have been characterized by NMR and SEC and assayed for in vitro and in vivo gene transfer.

Results

The animal experiments showed that the new copolymers are able to significantly increase the transfection efficiency of plasmid DNA after intramuscular injection.

Conclusions

These results indicate that the capacity to enhance plasmid DNA transfection in skeletal muscle is not restricted to pEO–pPO–pEO arrangements.

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