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Biomaterials. 2009 Oct;30(29):5815-24. doi: 10.1016/j.biomaterials.2009.06.057. Epub 2009 Jul 16.

Amine-modified hyperbranched polyesters as non-toxic, biodegradable gene delivery systems.

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Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, D-35037 Marburg, Germany.


For chronic non-viral gene therapy, biodegradable carriers with low cytotoxicity are essential. To create a series of non-toxic and biodegradable gene carriers, hyperbranched polymers based on 2,2-bis-(methylol)propionic acid (bis-MPA); (Boltorn H) were modified by introducing tertiary amines. The terminal OH groups were modified with diethylaminopropylamine (DEAPA) by carbonyldiimidazole (CDI) chemistry. The resulting polymers were characterized by (1)H, (13)C NMR, IR and GPC. Degradability and degradation rate were investigated with respect to the degree of amine substitution. The toxicity of all hyperbranched polyesters was generally very low compared to polyethyleneimine (PEI). Measurements of size and zeta potential showed that small nano-complexes with a positive zeta potential were formed. Dependency of the degree of amine substitution on interaction with DNA was studied by agarose gel retardation assay and ethidium bromide exclusion assay. Influence of the amine substitution on transfection efficiency of the different polymers demonstrated that a certain amine substitution degree was required to achieve transfection efficiency. These carriers provide degradability, very low toxicity and the ability to transfect cells which can be influenced by the degree of amine substitution.

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