Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform

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• 作者：Hiroe Yamada ; Brigitta Loretz ; Claus-Michael Lehr
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：May 12, 2014
• 年：2014
• 卷：15
• 期：5
• 页码：1753-1761
• 全文大小：455K
• 年卷期：v.15,no.5(May 12, 2014)
• ISSN：1526-4602

文摘

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-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. The optimal starch-graft-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.