Evaluation of Hyperbranched Poly(amino ester)s of Amine Constitutions Similar to Polyethylenimine for DNA Delivery

摘要

New hyperbranched poly(amino ester)s were synthesized via A_3+2BB'B" approach,represented by the Michael addition polymerization of trimethylol-propane triacrylate (TMPTA) (A_3-type monomers) with a double molar 1-(2-aminoethyl)piperazine (AEPZ) (BB'B"-type monomer) performed in chloroform at ambient temperature.The results obtained by in situ monitoring the polymerization using NMR and MS indicated that hyperbranched poly(TMPTA1-AEPZ2) was formed via a A(B'B")_2 intermediate,and the B" (the formed 2 deg amine) was kept intact in the reaction.Therefore,poly(TMPTA1-AEPZ2) contained secondary and tertiary amines in the core and primary amines in the periphery similar to polyethylenimine (PEI).The chemistry of protonated poly(TMPTA1-AEPZ2) was further confirmed by ~(13)C NMR,and the molecular weight,the radius of gyration (R_g),and the hydrodynamic radius (R_h) were determined using GPC,small-angle X-ray scattering (SAXS),and laser dynamic light scattering (LDLS),respectively.The ratio of R_g/R_h of ca.1.1 verified the hyperbranched structure.Protonated hyperbranched poly(TMPTA1-AEPZ2) is degradable and less cytotoxic as compared with PEI (25 K).Gel electrophoresis reflected that stable complexes could be formed from protonated hyperbranched poly(TMPTA1-AEPZ2) and DNA,and the size and xi-potential of the complexes were characterized.Remarkably,protonated hyperbranched poly(TMPTA1-AEPZ2) showed transfection efficiency comparable to PEI (25 k) for in vitro DNA delivery.