A degradable hyperbranched poly(ester amine) based on poloxamer diacrylate and polyethylenimine as a gene carrier.
Polyethylenimine (PEI) is a well-known cationic polymer which has high transfection efficiency due to its buffering effect. However, nondegradability, cytotoxicity, aggregation, and short-circulation time in vivo still need to be overcome for a successful gene delivery. Degradable, hyperbranched poly(ester amine)s (PEAs) based on poloxamer diacrylate and low molecular weight branched PEI, were successfully synthesized and evaluated as a nonviral gene carrier. The PEAs were obtained in significant yields through Michael type addition reaction of diacrylate monomers and low molecular weight branched PEI. Analysis of degradation products by the reduction in molecular weight demonstrated that PEAs degrade in a controlled fashion. The PEA showed good DNA binding ability and the sizes of complexes under physiological condition were below 150 nm, implicating its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (A549, 293T, and HepG2) compared with PEI 25K. PEAs showed much higher transfection efficiencies in three cell lines compared with PEI 25K and PEI 1.8K, and revealed little serum dependency in A549 cell line when the content of poloxamer in the PEA was increased up to 30%.
Kim
Tae Hee
TH
School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Cook
Seung Eun
SE
Arote
Rohidas B
RB
Cho
Myung-Haing
MH
Nah
Jae Woon
JW
Choi
Yun Jaie
YJ
Cho
Chong Su
CS
D000179:Acrylates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D020442:Poloxamer / Q000737:chemistry*; D011073:Polyamines / Q000138:chemical synthesis / Q000378:metabolism*; D011091:Polyesters / Q000138:chemical synthesis / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
D000179:Acrylates; D011073:Polyamines; D011091:Polyesters; C516446:poly(caprolactone-block-ethyleneimine); D020442:Poloxamer; D011094:Polyethyleneimine; D004247:DNA