Tseng Wen-Chi, Jong Chai-Min
Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
Biomacromolecules. 2003 Sep-Oct;4(5):1277-84. doi: 10.1021/bm034083y.
In vivo instability of a polycationic vector limits its efficacy after systemic administration. Conjugation of hydrophilic polymers with neutral charge onto polycationic vectors has been used to improve the stability by reducing the interactions between the vectors and the blood components, such as serum albumin. In this study, dextrans of molecular weight 10000 (dex-10000) and 1500 (dex-1500) were used to produce various degrees of grafting on linear and branched polyethylenimines (PEI), and the dextran-grafted polymers were used to prepare DNA-polymer complexes. The changes in size and in zeta-potential and the extent of DNA release after the exposure of the complexes to bovine serum albumin (BSA) were used to evaluate the stability of the complexes prepared at various ratios of DNA to polymer. Only the use of dextran-grafted branched PEI was found to be effective to improve the stability of the complexes in the presence of BSA. Dex-10000 was noted to provide a slightly better shielding than dex-1500 against the aggregation caused by BSA and helped maintain the sizes within 200 nm and the zeta-potentials close to neutral. It is thus concluded that the dextran-grafted branched PEI improved the stability of the DNA-polymer complexes and showed potential to conjugate with ligands for in vivo targeted gene delivery.
聚阳离子载体在体内的不稳定性限制了其全身给药后的疗效。将带中性电荷的亲水性聚合物与聚阳离子载体共轭，已被用于通过减少载体与血液成分（如血清白蛋白）之间的相互作用来提高稳定性。在本研究中，使用分子量为10000（dex-10000）和1500（dex-1500）的葡聚糖在直链和支链聚乙烯亚胺（PEI）上进行不同程度的接枝，并用葡聚糖接枝聚合物制备DNA-聚合物复合物。通过复合物在暴露于牛血清白蛋白（BSA）后尺寸和zeta电位的变化以及DNA释放程度，来评估在不同DNA与聚合物比例下制备的复合物的稳定性。结果发现，只有使用葡聚糖接枝的支链PEI才能有效地提高复合物在BSA存在下的稳定性。与dex-1500相比，dex-10000在防止BSA引起的聚集方面表现出稍好的屏蔽作用，并有助于将尺寸维持在200nm以内，zeta电位接近中性。因此得出结论，葡聚糖接枝的支链PEI提高了DNA-聚合物复合物的稳定性，并显示出与配体共轭用于体内靶向基因递送的潜力。
