Liu Chang, Luo Qi, Tu YingFeng, Wang GuiLing, Liu YingChun, Xie Ying
a Department of Pharmaceutics, State Key Laboratory of Natural and Biomimetic Drugs , School of Pharmaceutical Sciences, Peking University , Beijing , People's Republic of China and.
b Soft Matter Research Center and Department of Chemistry, Zhejiang University , Hangzhou , Zhejiang , People's Republic of China.
J Microencapsul. 2015;32(8):745-54. doi: 10.3109/02652048.2015.1073390. Epub 2015 Aug 21.
Doxorubicin (DOX) is widely used as an antitumor model drug in liposomes because of its high encapsulation efficiency. The cell-penetrating peptide (CPP) has potential applications in drug delivery systems. However, we discovered that the encapsulation efficiency of DOX decreased with increasing modification density of CPP on liposomes. To explore the interaction mechanisms of CPP-modified liposomes (CPPL) for DOX loading, X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were utilised, and theoretical calculations based on molecular dynamics simulation were performed. Results showed that the monomeric intermolecular interaction between CPP and DOX, in which the guanidinium group of CPP was parallel to the planar aromatic chromophore of DOX, depending on the cation-pi interaction and hydrogen bonds, weakened the tendency of DOX transporting into the internal medium from the liposomal external medium. Analysis of the interaction between CPP and DOX at the molecular level provided theoretical guidance for the further development of CPPL.
由于阿霉素（DOX）具有较高的包封率，它被广泛用作脂质体中的抗肿瘤模型药物。细胞穿透肽（CPP）在药物递送系统中具有潜在应用。然而，我们发现随着CPP在脂质体上修饰密度的增加，DOX的包封率降低。为了探究CPP修饰脂质体（CPPL）负载DOX的相互作用机制，我们利用了X射线衍射、傅里叶变换红外光谱和拉曼光谱，并基于分子动力学模拟进行了理论计算。结果表明，CPP与DOX之间的单体分子间相互作用，其中CPP的胍基与DOX的平面芳香发色团平行，依赖于阳离子-π相互作用和氢键，削弱了DOX从脂质体外部介质转运到内部介质的趋势。在分子水平上对CPP与DOX相互作用的分析为CPPL的进一步发展提供了理论指导。
