Sadzuka Yasuyuki, Tsuruda Tomoko, Sonobe Takashi
Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Yakugaku Zasshi. 2005 Jan;125(1):149-57. doi: 10.1248/yakushi.125.149.
It is known that polyethyleneglycol (PEG) modification of the liposome surface leads to the formation of a fixed aqueous layer around the liposomes due to interaction between the PEG polymer and water molecules, which prevents the attraction of opsonins. When a combination of PEG-distearolyglycerol (PEG-DSG) whose characteristics are remarkably different is used, interaction between molecules occurs, leading to increased fixed aqueous layer thickness (FALT). From this speculation, we studied the effect of both modification of PEG900-DSG and PEG2000-DSG modified liposome on FALT, cell uptake and biodistribution. The FALT of mixed PEG modified liposome increased, compared to that of each single PEG modified liposome. In this mixed modification, maximum FALT was shown at liposome modified by added PEG-2000:PEG-900=2:1. This most suitable additional ratio was equal to actual incorporated ratio. On the other hand, cell uptake of mixed modified liposome containing doxorubicin (DOX) was similar with that of PEG2000 modified liposome. Furthermore, mixed PEG modification of liposome was tendency to increase cytotoxicity, compared to that of other modifications. After DOX contained liposome treatment, DOX distribution in the tumor and antitumor activity of DOX increase by mixed PEG modification. In conclusion, it was suggested that mixed PEG liposome (PEG-2000:PEG-900=2:1) was useful for cancer chemotherapy.
已知对脂质体表面进行聚乙二醇（PEG）修饰会因PEG聚合物与水分子之间的相互作用而在脂质体周围形成固定的水层，这可防止调理素的吸附。当使用特性明显不同的聚乙二醇-二硬脂酰甘油（PEG-DSG）组合时，分子间会发生相互作用，导致固定水层厚度（FALT）增加。基于此推测，我们研究了PEG900-DSG和PEG2000-DSG修饰的脂质体对FALT、细胞摄取和生物分布的影响。与每种单一PEG修饰的脂质体相比，混合PEG修饰的脂质体的FALT增加。在这种混合修饰中，添加PEG-2000:PEG-900 = 2:1修饰的脂质体显示出最大的FALT。这个最合适的添加比例与实际掺入比例相等。另一方面，含阿霉素（DOX）的混合修饰脂质体的细胞摄取与PEG2000修饰的脂质体相似。此外，与其他修饰相比，脂质体的混合PEG修饰有增加细胞毒性的趋势。含DOX的脂质体处理后，混合PEG修饰可使DOX在肿瘤中的分布及DOX的抗肿瘤活性增加。总之，提示混合PEG脂质体（PEG-2000:PEG-900 = 2:1）对癌症化疗有用。
