Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, L'Hospitalet de Llobregat, Spain; ALBA Synchrotron Light Source, Cerdanyola del Vallès, Spain.
Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Nanomedicine. 2019 Apr;17:198-209. doi: 10.1016/j.nano.2019.01.010. Epub 2019 Jan 30.
Poly(propylene imine) dendrimers have been shown to be promising 3-dimensional polymers for the use in the pharmaceutical and biomedical applications. Our aims of this study were first, to synthesize a novel type of dendrimer with poly(propylene imine) core and maltose-histidine shell (G4HisMal) assessing if maltose-histidine shell can improve the biocompatibility and the ability to cross the blood-brain barrier, and second, to investigate the potential of G4HisMal to protect Alzheimer disease transgenic mice from memory impairment. Our data demonstrate that G4HisMal has significantly improved biocompatibility and ability to cross the blood-brain barrier in vivo. Therefore, we suggest that a maltose-histidine shell can be used to improve biocompatibility and ability to cross the blood-brain barrier of dendrimers. Moreover, G4HisMal demonstrated properties for synapse and memory protection when administered to Alzheimer disease transgenic mice. Therefore, G4HisMal can be considered as a promising drug candidate to prevent Alzheimer disease via synapse protection.
聚丙稀亚胺树状聚合物已被证明是一种很有前途的 3 维聚合物，可用于药物和生物医学应用。本研究的目的首先是合成一种新型的以聚丙稀亚胺为核、麦芽糖-组氨酸为壳的树状聚合物（G4HisMal），评估麦芽糖-组氨酸壳是否能提高生物相容性和穿越血脑屏障的能力；其次，研究 G4HisMal 是否能保护阿尔茨海默病转基因小鼠免受记忆损伤。我们的数据表明，G4HisMal 显著提高了体内的生物相容性和穿越血脑屏障的能力。因此，我们认为麦芽糖-组氨酸壳可用于提高树状聚合物的生物相容性和穿越血脑屏障的能力。此外，G4HisMal 对阿尔茨海默病转基因小鼠的突触和记忆保护具有特性。因此，G4HisMal 可以被认为是一种有前途的药物候选物，通过保护突触来预防阿尔茨海默病。
