Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity.
Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity.
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DOI：
10.2147/ijn.s27028
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发表时间：
2011
影响因子：
8
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Shao N;Su Y;Hu J;Zhang J;Zhang H;Cheng Y
聚酰胺胺（PAMAM）和聚丙烯亚胺（PPI）树枝状聚合物是可商购的并且在药物科学和生物医学工程中最广泛使用的树枝状聚合物。在本研究中，第3代PAMAM和第4代PPI树枝状聚合物的负载和释放行为进行了比较，使用保泰松作为模型药物的表面胺基团的量相同（32个树枝状聚合物）。通过核磁共振氢谱和核Overhauser效应技术对树枝状大分子-保泰松复合物进行了表征，并对每种树枝状大分子的细胞毒性进行了评价。水溶解度结果表明，第3代PAMAM树枝状聚合物具有更高的负载能力对保泰松相比，第4代PPI树枝状聚合物在高保泰松树枝状聚合物进料比。药物从第3代PAMAM基质的释放比从第4代PPI树枝状聚合物的释放慢得多。此外，第3代PAMAM树枝状聚合物对MCF-7和A549细胞系的毒性比第4代PPI树枝状聚合物低至少50倍。尽管核Overhauser效应核磁共振结果显示具有更疏水内部的第4代PPI树枝状聚合物包封更多保泰松，但PPI树枝状聚合物-保泰松包合物在水溶液中不稳定，这在药物开发期间提出了很大的挑战。
Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development.