Synthesis and evaluation of amphiphilic poly(tetrahydrofuran-b-ethylene oxide) copolymers for DNA delivery into skeletal muscle

Pharm Res. 2008 Dec;25(12):2963-71. doi: 10.1007/s11095-008-9698-9. Epub 2008 Sep 3.

Abstract

Purpose: Amphiphilic triblock copolymers such as the pluronic poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) L64 (pEO(13)-pPO(30)-pEO(13)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butylene Glycols / administration & dosage
  • Butylene Glycols / chemical synthesis*
  • Butylene Glycols / chemistry
  • DNA / administration & dosage*
  • Gene Transfer Techniques*
  • Humans
  • Muscle, Skeletal / metabolism*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / chemistry
  • Polymers / administration & dosage
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Butylene Glycols
  • Polymers
  • poly(tetrahydrofuran)
  • Polyethylene Glycols
  • DNA