Design and synthesis of cationic drug carriers based on hyperbranched poly(amine-ester)s.
Novel cationic drug carriers based on hyperbranched poly(amine-ester)s were successfully prepared through proton-transfer polymerization. Both vinyl and epoxy groups of commercially available glycidyl methacrylate monomer could be polymerized through oxyanionic initiation of triethanolamine in the presence of potassium hydride catalysis. By changing the molar ratios of triethanolamine/glycidyl methacrylate or potassium hydride/triethanolamine, we obtained a series of hyperbranched poly(amine-ester)s. The generation of highly branched poly(amine-ester)s was confirmed by (13)C DEPT-135 NMR and 2D NMR techniques, and their degrees of branching were found to be 0.47 to 0.68. The structure and properties of hyperbranched poly(amine-ester)s were analyzed by dynamic light scattering, gel permeation chromatography, Fourier transformed infrared, differential scanning calorimeter, and zeta-potential measurements. Methyl tetrazolium (MTT) assay suggested that the cell viability after 48 h incubation with hyperbranched poly(amine-ester) concentrations up to 1 mg/mL remained nearly 100% compared with the untreated cells. The high cellular uptake of these cationic polymers was confirmed by flow cytometry and confocal laser scanning microscopy. Furthermore, conjugation of a model hydrophobic anticancer drug chlorambucil to hyperbranched poly(amine-ester)s inhibited the proliferation of MCF-7 breast cancer cells. MTT assay indicated that the chlorambucil dose required for 50% cellular growth inhibition against MCF-7 cells was 120 microg/mL. All of these results show that hyperbranched poly(amine-ester)s are promising materials for drug delivery.
Pang
Yan
Y
School of Chemistry and Chemical Engineering and Instrumental Analysis Center, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
Zhu
Qi
Q
Liu
Jinyao
J
Wu
Jieli
J
Wang
Ruibin
R
Chen
Suyun
S
Zhu
Xinyuan
X
Yan
Deyue
D
Huang
Wei
W
Zhu
Bangshang
B
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002412:Cations; D004337:Drug Carriers; D004952:Esters; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D041681:NIH 3T3 Cells; D011073:Polyamines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D002412:Cations; D004337:Drug Carriers; D004952:Esters; D011073:Polyamines