Evaluation of hyperbranched poly(amino ester)s of amine constitutions similar to polyethylenimine for DNA delivery.
New hyperbranched poly(amino ester)s were synthesized via A3 + 2BB'B' ' approach, represented by the Michael addition polymerization of trimethylol-propane triacrylate (TMPTA) (A3-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 degrees 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 13C NMR, and the molecular weight, the radius of gyration (Rg), and the hydrodynamic radius (Rh) were determined using GPC, small-angle X-ray scattering (SAXS), and laser dynamic light scattering (LDLS), respectively. The ratio of Rg/Rh 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.
Wu
Decheng
D
Institute of Materials Research and Engineering, 3 Research Link, Singapore 117602.
Liu
Ye
Y
Jiang
Xuan
X
Chen
Ling
L
He
Chaobin
C
Goh
Suat Hong
SH
Leong
Kam W
KW
D000179:Acrylates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D002725:Chloroform / Q000737:chemistry; D002845:Chromatography; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D004952:Esters / Q000737:chemistry*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D006868:Hydrolysis; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011522:Protons; D012542:Scattering, Radiation; D013696:Temperature; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors
D000179:Acrylates; D001672:Biocompatible Materials; D004952:Esters; D010879:Piperazines; D011108:Polymers; D011522:Protons; D013778:Tetrazolium Salts; D013844:Thiazoles; C033005:aminoethylpiperazine; C027993:trimethylolpropane triacrylate; D002725:Chloroform; D011094:Polyethyleneimine; D004247:DNA; C022616:thiazolyl blue