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一项关于聚酰胺-胺(PAMAM)树枝状大分子对二棕榈酰磷脂酰胆碱(DPPC)模型脂质膜影响的差示扫描量热法(DSC)和拉曼光谱研究。

A DSC and Raman spectroscopy study on the effect of PAMAM dendrimer on DPPC model lipid membranes.

作者信息

Gardikis Konstantinos, Hatziantoniou Sophia, Viras Kyriakos, Wagner Matthias, Demetzos Costas

机构信息

Department of Pharmaceutical Technology, School of Pharmacy, Panepistimiopolis, Zografou 15771, University of Athens, Athens, Greece.

出版信息

Int J Pharm. 2006 Aug 2;318(1-2):118-23. doi: 10.1016/j.ijpharm.2006.03.023. Epub 2006 Mar 29.

Abstract

The interaction between PAMAM (polyamidoamine) dendrimer generation 4 (G4) and 3,5 (G3,5) with model lipid membranes composed of dipalmytoylphosphatidylcholine (DPPC) has been investigated. Differential scanning calorimetry (DSC) and Raman spectroscopy were applied to assess the thermodynamic changes caused by PAMAM G4 and G3,5 and to specify the exact location of these dendrimers into the DPPC lipid bilayer. DSC thermograms indicated that the maximum percentages of PAMAM G4 and of G3,5 that can be incorporated in the DPPC membrane without deranging its integrity were 5% and 3%, respectively. The Raman intensity ratios I(2935/2880), I(2844/2880) and I(1090/1130) cm(-1) showed the degree of the fluidity of the lipid bilayer, while the absorption at 715 cm(-1) showed a strong interaction of PAMAM G4 and G3,5 with the polar head group of phospholipid. The results showed that the incorporation of the PAMAM G4 and G3,5 dendrimers in DPPC bilayers causes a concentration dependent increase of the membrane fluidity and that the bilayers interact strongly with both the lipophilic part and the polar head group of the phospholipids. Due to the current weak knowledge relating to the mechanism(s) under which dendrimers interact with lipidic membranes and transport through cells, these results may justify the tendency of dendrimers to disrupt biological membranes. The findings from this study could also prove helpful to rationally design new liposomal drug carriers for bioactive molecules by combining dendrimeric and liposomal technologies.

摘要

已对第4代聚酰胺-胺(PAMAM)树枝状大分子(G4)和3,5(G3,5)与由二棕榈酰磷脂酰胆碱(DPPC)组成的模型脂质膜之间的相互作用进行了研究。应用差示扫描量热法(DSC)和拉曼光谱来评估由PAMAM G4和G3,5引起的热力学变化,并确定这些树枝状大分子在DPPC脂质双层中的精确位置。DSC热谱图表明,在不破坏其完整性的情况下,可掺入DPPC膜中的PAMAM G4和G3,5的最大百分比分别为5%和3%。拉曼强度比I(2935/2880)、I(2844/2880)和I(1090/1130) cm(-1)显示了脂质双层的流动性程度,而715 cm(-1)处的吸收显示PAMAM G4和G3,5与磷脂的极性头部基团有强烈相互作用。结果表明,PAMAM G4和G3,5树枝状大分子掺入DPPC双层中会导致膜流动性随浓度增加,并且双层与磷脂的亲脂部分和极性头部基团都有强烈相互作用。由于目前对树枝状大分子与脂质膜相互作用及通过细胞运输的机制了解不足,这些结果可能解释了树枝状大分子破坏生物膜的倾向。本研究的结果也可能有助于通过结合树枝状大分子和脂质体技术,合理设计用于生物活性分子的新型脂质体药物载体。

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