Mullen Douglas G, Desai Ankur, van Dongen Mallory A, Barash Mark, Baker James R, Banaszak Holl Mark M
Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109 ; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109.
Macromolecules. 2012 Jun 26;45(12):5316-5320. doi: 10.1021/ma300485p. Epub 2012 Jun 11.
Poly(amidoamine) (PAMAM) dendrimer are branched polymers with low degrees of heterogeneity. Current synthesis methods, however, result in substantial batch variability. We present our optimized procedure for post-synthesis (and post-market) purification of a generation 5 PAMAM dendrimer by membrane dialysis and demonstrate its effectiveness and limitations using a representative lot of biomedical grade dendrimer. This method successfully removes trailing generation defect structures, thereby reducing the heterogeneity of the material (PDI reduced from 1.04 to 1.02). Optimized analytical techniques to characterize the unpurified and purified dendrimer are also detailed. The efficiency of the purification method is successfully monitored by these analytics and dendrimer parameters that are critical for subsequent modification reactions and biological evaluation (M(n), M(w), PDI, average number of end groups) obtained. To provide better definition of the variability that should be expected between lots of synthesized material, HPLC traces for three additional commercial lots of dendrimer are also presented.
聚（酰胺胺）（PAMAM）树枝状大分子是具有低异质性程度的支化聚合物。然而，目前的合成方法会导致大量的批次变异性。我们展示了通过膜透析对第5代PAMAM树枝状大分子进行合成后（以及上市后）纯化的优化程序，并使用一批具有代表性的生物医学级树枝状大分子证明了其有效性和局限性。该方法成功去除了后续代的缺陷结构，从而降低了材料的异质性（多分散指数从1.04降至1.02）。还详细介绍了用于表征未纯化和纯化树枝状大分子的优化分析技术。通过这些分析方法以及对后续修饰反应和生物学评估至关重要的树枝状大分子参数（数均分子量、重均分子量、多分散指数、端基平均数）成功监测了纯化方法的效率。为了更好地定义合成材料批次之间预期的变异性，还展示了另外三批市售树枝状大分子的高效液相色谱图。
