Physiochemical Properties of Low and High Molecular Weight Poly(ethylene glycol)-Grafted Poly(ethylene imine) Copolymers and Their Complexes with Oligonucleotides
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- 作者：Martin Glodde ; Shashank R. Sirsi ; and Gordon J. Lutz
- 刊名：Biomacromolecules
- 出版年：2006
- 出版时间：January 2006
- 年：2006
- 卷：7
- 期：1
- 页码：347 - 356
- 全文大小：811K
- 年卷期：v.7,no.1(January 2006)
- ISSN：1526-4602
文摘
Inefficient delivery of antisense oligonucleotides (AOs) to target cell nuclei remains as the foremost limitation totheir usefulness. Copolymers of cationic poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) have beenwell-studied for delivery of plasmids. However, the properties of PEG-PEI-AO polyplexes have not beencomprehensively investigated. Therefore, we synthesized a series of PEG-PEI copolymers and evaluated theirphysiochemical properties alone and when complexed with AO. The Mw of PEG was found to be the maindeterminant of polyplex size, via its influence on particle aggregation. DLS measurements showed that whenPEG5000 was grafted to PEI2K and PEI25K, polyplex diameters were extremely small (range 10-90 nm) withminimal aggregation. In contrast, when PEG550 was grafted to PEI2K and PEI25K, polyplexes appeared asmuch larger aggregates (~250 nm). As expected, the surface charge (
potential) was higher for polyplexescontaining PEI25K than those containing PEI2K, but decreased with increased levels of PEG grafting. Surprisingly,within the physiological range (pH 7.5-5), the buffering capacity of all copolymers was nearly equivalent to thatof unsubstituted PEI2K or PEI25K, and was barely influenced by PEGylation. The stability of polyplexes wasevaluated using a heparin polyanion competition assay. Unexpectedly, polyplexes containing PEI2K showed stabilityequal to or greater than that of PEI25K polyplexes. The level of PEG grafting also had a dramatic effect onpolyplex stability. The relationships established between molecular formulations and polyplex size, aggregation,surface charge, and stability should provide a useful guide for future studies aimed at optimizing polymer-mediatedAO delivery in cell and animal studies. A summary of the relationships between polyplex structures and recentstudies of their transfection capacity is provided.
potential) was higher for polyplexescontaining PEI25K than those containing PEI2K, but decreased with increased levels of PEG grafting. Surprisingly,within the physiological range (pH 7.5-5), the buffering capacity of all copolymers was nearly equivalent to thatof unsubstituted PEI2K or PEI25K, and was barely influenced by PEGylation. The stability of polyplexes wasevaluated using a heparin polyanion competition assay. Unexpectedly, polyplexes containing PEI2K showed stabilityequal to or greater than that of PEI25K polyplexes. The level of PEG grafting also had a dramatic effect onpolyplex stability. The relationships established between molecular formulations and polyplex size, aggregation,surface charge, and stability should provide a useful guide for future studies aimed at optimizing polymer-mediatedAO delivery in cell and animal studies. A summary of the relationships between polyplex structures and recentstudies of their transfection capacity is provided.