Shuai Xintao, Merdan Thomas, Unger Florian, Kissel Thomas
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
Bioconjug Chem. 2005 Mar-Apr;16(2):322-9. doi: 10.1021/bc0498471.
Soluble supramolecular inclusion complexes were formed by threading alpha-cyclodextrin (alpha-CD) molecules over poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) chains of ternary block copolymers of PEG, PCL and polyethylenimine (PEI). Characteristic shifts of PCL absorptions in FTIR, (1)H NMR and UV spectra strongly suggest that alpha-CD is threaded over PEG and PCL blocks. Due to the reduced hydrophobic interaction between PCL blocks, the resulting supramolecular complexes displayed a dramatically increased solubility, in comparison with the ternary block copolymers. Their ability to complex DNA was almost as efficient as that of branched PEI 25 kDa, as shown in the ethidium bromide fluorescence quenching experiments. Resulting DNA polyplexes displayed a size of around 200 nm and a neutral surface charge. Microscopy studies in 3T3 fibroblasts revealed an efficient cellular uptake. Transfection efficiencies of inclusion complexes were in the same order of magnitude as PEI. In contrast to PEI a 100x lower toxicity was observed by MTT-assay, allowing the administration of nitrogen-to-phosphate ratios of up to 20. These new gene delivery systems merit further characterization under in vivo conditions.
通过将α-环糊精（α-CD）分子穿绕在聚乙二醇（PEG）、聚己内酯（PCL）和聚乙烯亚胺（PEI）的三元嵌段共聚物的PEG链和PCL链上，形成了可溶性超分子包合物。傅里叶变换红外光谱（FTIR）、核磁共振氢谱（¹H NMR）和紫外光谱中PCL吸收峰的特征位移强烈表明α-CD穿绕在PEG和PCL嵌段上。由于PCL嵌段之间的疏水相互作用减弱，与三元嵌段共聚物相比，所得超分子复合物的溶解度显著增加。如溴化乙锭荧光猝灭实验所示，它们与DNA复合的能力几乎与25 kDa的支化PEI一样有效。所得DNA多聚体的大小约为200 nm，表面电荷呈中性。对3T3成纤维细胞的显微镜研究显示其具有高效的细胞摄取能力。包合物的转染效率与PEI处于同一数量级。与PEI相比，通过MTT测定法观察到的毒性低100倍，允许施用高达20的氮磷比。这些新型基因递送系统值得在体内条件下进一步表征。
