Design of Starch-<i>graft</i>-PEI Polymers:
An Effective and Biodegradable Gene Delivery Platform
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Abstract
Starch and starch derivatives are
widely utilized pharmaceutical
excipients. The concept of this study was to make use of starch as
a biodegradable backbone and to modify it with low-toxic, but poor
transfecting low molecular weight polyethylenimine (PEI) in order
to achieve better transfection efficacy while maintaining enzymatic
degradability. A sufficiently controllable conjugation could be achieved
via a water-soluble intermediate of oxidized starch and an optimized
reaction protocol. Systematic variation of MW fraction of the starch
backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded
a series of starch-<i>graft</i>-PEI copolymers. Following
purification and chemical characterization, nanoscale complexes with
plasmid DNA were generated and studied regarding cytotoxicity and
transfection efficacy. The optimal starch-<i>graft</i>-PEI
polymers consisted of >100 kDa MW starch and contained 30% (wt)
of
PEI, showing similar transfection levels as 25 kDa bPEI, and being
less cytotoxic and enzymatically biodegradable