Poly(ethylenimine-co-L-lactamide-co-succinamide):: A biodegradable polyethylenimine derivative with an advantageous pH-dependent hydrolytic degradation for gene delivery
Poly(ethylenimine-co-L-lactamide-co-succinamide):: A biodegradable polyethylenimine derivative with an advantageous pH-dependent hydrolytic degradation for gene delivery
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DOI：
10.1021/bc0255135
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发表时间：
2002-07-01
影响因子：
4.7
通讯作者：
Kissel, T
中科院分区：
文献类型：
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作者：
Petersen, H;Merdan, T;Kissel, T
通过低分子量（MW）聚乙烯亚胺（PEI, 1200 Da）与低聚物（l -乳酸-琥珀酸）（OLSA, 1000 Da）连接，合成了一个可生物降解的基因转移载体。所得共聚物P(EI-co-LSA) （8 kDa）可溶于水，并通过碱催化水解裂解酰胺键降解。至于其作为基因转移剂的应用，聚合物表现出有趣的pH依赖性降解。在pH值为5时，当dna酶高度活跃时，降解的速度比生理pH值为7.4时慢。PEI和P（EI-co-LSA）与质粒DNA自发形成复合物。与PEI形成的配合物不稳定且聚集，形成的颗粒可达1 μ m水动力直径，而P（EI-co-LSA）形成的配合物尺寸约为150 nm，尺寸分布较窄。后一种配合物由于其高表面电荷（zeta电位+ 18 mV）而稳定。与低分子量PEI类似，该共聚物具有低毒性。同时，与低分子量PEI相比，共聚物的转染活性显著增强。这使得P（EI-co-LSA）成为生物相容性和生物可降解性日益重要的长期基因治疗的有希望的候选者。
A biodegradable gene transfer vector has been synthesized by linking several low molecular weight (MW) polyethylenimine (PEI, 1200 Da) blocks using an oligo(L-lactic acid-co-succinic acid) (OLSA, 1000 Da). The resulting copolymer P(EI-co-LSA) (8 kDa) is soluble in water and degrades via base-catalyzed hydrolytic cleavage of amide bonds. With regard to its application as a gene transfer agent, the polymer showed an interesting pH dependency of degradation. At pH 5, when DNases are highly active, the degradation proceeds at a slower rate than at a physiological pH of 7.4. PEI and P(EI-co-LSA) spontaneously formed complexes with plasmid DNA. Whereas the complexes formed with PEI were not stable and aggregated, forming particles of up to 1 mum hydrodynamic diameter, P(EI-co-LSA) formed complexes, which were about 150 nm in size and of narrow size distribution. The latter complexes were stable, due to their high surface charge (zeta-potential + 18 mV). Similar to low MW PEI, the copolymer exhibited a. low toxicity profile. At the same time, the copolymer showed a significant enhancement of transfection activity in comparison to the low MW PEI. This makes P(EI-co-LSA) a promising candidate for long-term gene therapy where biocompatibility and biodegradability become increasingly important.