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Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

Authors Shao N, Su Y, Hu J, Zhang J, Zhang H, Cheng Y

Published 16 December 2011 Volume 2011:6 Pages 3361—3372

DOI https://doi.org/10.2147/IJN.S27028

Review by Single-blind

Peer reviewer comments 5

Naimin Shao1, Yunzhang Su1, Jingjing Hu2, Jiahai Zhang3, Hongfeng Zhang1, Yiyun Cheng1,4
1School of Life Sciences, East China Normal University, Shanghai, 2CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei,  3School of Life Sciences, University of Science and Technology of China, Hefei, 4Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai, China

Background: 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.
Methods: The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated.
Results: 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.
Conclusion: 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.

Keywords: dendrimer, polyamidoamine, polypropylenimine, drug delivery, cytotoxicity

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