Liu Yu, Steele Terry, Kissel Thomas
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, 35037 Marburg, Germany.
Macromol Rapid Commun. 2010 Sep 1;31(17):1509-15. doi: 10.1002/marc.201000337. Epub 2010 Jul 27.
Water-soluble hyper-branched poly(ethylenimine)-graft-poly(caprolactone)-block-monomethoxyl-poly(ethylene glycol) cationic copolymers (hy-PEI-PCL-mPEG) have shown potential for gene delivery. The degradation behavior of this type of copolymer is studied. Effects of the molecular weight of the hyper-branched PEI (hy-PEI), and the length of the mPEG and PCL blocks are investigated. The degradation is mainly monitored by the changes of molecular weight by GPC-MALLS. The molecular weight changes of the copolymers in different aqueous solutions have been characterized as a function of incubation time at 37°C from 0 to 45 d. The micelle size and pH value have also been recorded accordingly to monitor the degradation in water. The investigation reveals that copolymers containing hy-PEI2k degrade faster than others containing hy-PEI10k and hy-PEI25k based on the same mPEG-PCL block, while copolymers those contain mPEG5k degrade faster than those containing mPEG2k and mPEG0.55k based on the same PCL segments and hy-PEI. An inhibitory effect of acidic conditions and acceleration in basic media have been found for degradation in different buffers. A higher ionic strength of the buffer accelerated the degradation. The molecular weight of copolymer is reduced to 95% within one day with 10 mg·mL(-1) of lipase while 70% remains with 5 mg·mL(-1) of lipase. These investigations suggest that the degradation of hy-PEI-PCL-mPEG can be designed and the degradation period is reasonable for gene-transfer in vivo.
水溶性超支化聚（乙烯亚胺）接枝聚（己内酯）-嵌段-单甲氧基聚（乙二醇）阳离子共聚物（hy-PEI-PCL-mPEG）已显示出基因递送的潜力。研究了这类共聚物的降解行为。考察了超支化聚（乙烯亚胺）（hy-PEI）的分子量、mPEG和PCL嵌段长度的影响。降解主要通过凝胶渗透色谱-多角度激光光散射联用仪（GPC-MALLS）监测分子量的变化。共聚物在不同水溶液中的分子量变化已被表征为在37℃下0至45天孵育时间的函数。还相应记录了胶束尺寸和pH值以监测在水中的降解。研究表明，基于相同的mPEG-PCL嵌段，含有hy-PEI2k的共聚物比含有hy-PEI10k和hy-PEI25k的共聚物降解更快，而基于相同的PCL链段和hy-PEI，含有mPEG5k的共聚物比含有mPEG2k和mPEG0.55k的共聚物降解更快。在不同缓冲液中发现酸性条件对降解有抑制作用，碱性介质中有加速作用。缓冲液较高的离子强度加速了降解。在10mg·mL(-1)脂肪酶作用下，共聚物的分子量在一天内降至95%，而在5mg·mL(-1)脂肪酶作用下，70%的分子量保留下来。这些研究表明，hy-PEI-PCL-mPEG的降解是可以设计的，并且降解期对于体内基因转移来说是合理的。
