Degradable poly(amino alcohol esters) as potential DNA vectors with low cytotoxicity

Biomacromolecules. 2003 Nov-Dec;4(6):1759-62. doi: 10.1021/bm034176f.

Abstract

The synthesis of a new degradable polymer system, poly(amino alcohol esters) and the resulting polymers' potential for use in gene transfection vectors are reported. The polymerization proceeded in a one step reaction from commercially available bis(secondary amines) monomers (N,N'-dimethyl-1,3-propanediamine and N,N'-dimethyl-1,6-hexanediamine, respectively) through nucleophilic addition to the diglycidyl ester of dicarboxylic acid (diglycidyl adipate). Poly(amino alcohol ester) 1 and 2 were synthesized with a yield of 89% and 91% with Mn = 24,800 and Mn = 36,400, respectively. Poly(amino alcohol ester) 1 degraded hydrolytically in phosphate buffer at pH 7.4 with a half-life of approximately 5 days. Both polymers readily self-assembled with plasmid DNA into nanometer-sized DNA/polymer complexes less than 180 nm diameter and are significantly less cytotoxic than the commonly used DNA delivery polymer, poly(ethylene imine) (PEI).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Alcohols / chemical synthesis
  • Animals
  • Biodegradation, Environmental
  • Cell Survival / drug effects
  • DNA / administration & dosage*
  • Genetic Therapy / methods
  • Materials Testing
  • Mice
  • Particle Size
  • Plasmids / administration & dosage
  • Polyesters / chemical synthesis*
  • Polyesters / pharmacology
  • Solubility
  • Transfection / methods*

Substances

  • Amino Alcohols
  • Polyesters
  • DNA