Degradable poly(amino alcohol esters) as potential DNA vectors with low cytotoxicity.
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).
Jon
Sangyong
S
Department of Chemical Engineering, E25-342, Massachusetts Institute of Technology, 77 Mass Ave, Cambridge, Massachusetts 02139, USA.
Anderson
Daniel G
DG
Langer
Robert
R
D016475:3T3 Cells; D000605:Amino Alcohols / Q000138:chemical synthesis; D000818:Animals; D001673:Biodegradation, Environmental; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods; D008422:Materials Testing; D051379:Mice; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage; D011091:Polyesters / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D014162:Transfection / Q000379:methods*
D000605:Amino Alcohols; D011091:Polyesters; D004247:DNA