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

Abstract:

: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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Reul R,Nguyen J,Kissel T

doi

10.1016/j.biomaterials.2009.06.057

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

5815-24

issue

29

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(09)00683-8

journal_volume

30

pub_type

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