紫杉醇透过细胞膜的药物吸收过程及其脂质体制备与紫杉醇/脂质相互作用密切相关.通过Langmuir膜技术和原子力显微镜(AFM)观测,研究了不同比例的二棕榈酰磷脂胆碱(DPPC)/紫杉醇(paclitaxel)二元混合系统在空气/水界面上的单分子层相互作用.对膜压-面积(π-A)曲线的测量和基于π-A曲线的混合性分析、热力学稳定性分析及可压缩性分析表明:紫杉醇和DPPC相互混合,不同分子间存在斥力,混合单分子层出现相分离.除紫杉醇摩尔分数(xpac)为0.4外,这些现象均随单分子层压缩增加到一定程度后出现反转;对xpac=0.4,不同分子间混合程度、斥力作用和单分子层中相分离均远超过其他混合比例的单分子层,且随单分子层压缩程度持续增加,不同分子间相互作用的影响远远超过压缩程度;xpac≤0.4时,脂质单分子层结构受紫杉醇影响较小,超过0.4后脂质单分子层结构遭到严重破坏.利用原子力显微镜对紫杉醇/DPPC单分子层进行了表面形貌观测,证实了Langmuir研究的结果.
The absorption of paclitaxel through cell membrane and the preparation of paclitaxel liposome are closely related with interactions between paclitaxel and lipids.The interactions between paclitaxel and dipalmitoyl phosphatidylcholine(DPPC) in mixed monolayers at the air/water interface have been studied by langmuir technique and atomic force microscopy(AFM).The surface pressure-area(π-A) curves have been measured.The miscibility analysis,thermodynamic stability analysis and compressibility analysis have been carried out based on π-A curves.The results indicate that paclitaxel and DPPC are miscible,repulsion exists between different molecules,and phase separation appears in mixed monolayers.Except for xpac(pa-clitaxel mole fraction xpac=0.4,all these states increase with the compression of monolayers to a certain ex-tent and then start to decrease.For xpac=0.4,the miscibility,repulsion and phase separation always increase with the compression of monolayer,and are much greater than those for all the other mixed monolayers with different xpac.For xpac=0.4,the influence of the interactions between different molecules on these states is much greater than the effect of the extent of the compression of monolayer.For xpac≤0.4,paclitaxel has a little influence on the structure of DPPC monolayer;for xpac0.4,the structure of DPPC monolayer is de-stroyed seriously.The morphology of paclitaxel/DPPC monolayers has been observed by AFM and is con sistent with the conclusion obtained by langmuir study.