S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Poly (amino ester) composed of poly (ethylene glycol) and aminosilane prepared by combinatorial chemistry as a gene carrier
- Issue Date
- Kluwer Academic/Plenum Publishers
- Pharmaceutical Research, Vol.25 No.4, pp.875-885
- Purpose. Application of combinatorial chemistry and high throughput screening for the synthesis and evaluation of mini-library of novel biodegradable poly (beta-amino ester)s (PAE)s composed of gamma-aminopropyl-triethoxysilane (APES) and poly (ethylene glycol) diacrylate (PEGDA) for gene delivery efficiency and safety in 293T and HeLa cells in the presence of and absence of serum. Materials and methods. PAEs were synthesized at different mole ratios of APES and PEGDA by Michael addition reaction and synthesis was confirmed by H-1 nuclear magnetic resonance (H-1-NMR). Ninety six ratios of polyplexes were evaluated for luciferase and MTS assay in 293T and HeLa cells in the presence of and absence of serum. Relationship between transfection efficiency and DNA binding ability of PAEs was studied by gel electrophoresis. Particle sizes and molecular weight of selected PAEs were measured by dynamic light scattering and gel permeation chromatography multi-angle light scattering, respectively. Results. H-1-NMR confirmed the synthesis of PAEs. In both cell lines, transfection efficiency and cell viability were increased for PAEs obtained from R106 (0.7:1, APES:PEGDA) to R121 (6:1, APES:PEGDA) with a marginal increase in APES concentration. Transfection pattern was uniform in the absence of and presence of serum. In both cell lines, PAE obtained from R121 demonstrated high transfection efficiency and low cytotoxicity as compared to polyethylenimine (25 KDa) and Lipofectamine. PAE obtained from R121 showed good DNA binding and condensation with average particle sizes of 133 nm. Conclusion. Addition of PEGDA over APES resulted in a novel PAE which has high safety and transfection efficiency. Transfection and cytotoxicity are very sensitive to monomer ratios and mainly governed by concentration of amine monomer.
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