Higashi Kenjirou, Mibu Fusako, Saito Kengo, Limwikrant Waree, Yamamoto Keiji, Moribe Kunikazu
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Eur J Pharm Sci. 2017 Mar 1;99:24-31. doi: 10.1016/j.ejps.2016.11.029. Epub 2016 Dec 1.
Ascorbyl 2,6-dipalmitate (ASC-DP) and distearoyl phosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) formed stable nanoparticles at a molar ratio of less than or equal to 2:1 after dispersing the solvent-evaporated film in water. The mean particle sizes measured by dynamic light scattering were within the range of ca. 100-160nm. Composition-dependent changes of the ASC-DP and DSPE-PEG molecular states within the film were analyzed by wide-angle X-ray diffraction and infrared (IR) and solid-state nuclear magnetic resonance (NMR) spectroscopy. Transmission electron microscopy (TEM) of nanoparticles revealed that ASC-DP/DSPE-PEG changed from a micelle to a disk and tubular structure as the molar ratio increased. Quantitative solution-state H NMR measurements elucidated the structure of nanoparticle in water; the core could be composed of ASC-DP and hydrophobic acyl chains of DSPE, whereas the hydrophilic PEG chains of DSPE-PEG on the surface form the hydration shell to stabilize the nanoparticle dispersion in water. Cytotoxicity of ASC-DP against cancer cell lines was observed by using ASC-DP/DSPE-PEG nanoparticles, and no cytotoxicity against normal cells was found. Thus, the ASC-DP/DSPE-PEG formulation, with tumor cell specific cytotoxicity, can be applicable for cancer monotherapy or in combination with other anticancer drugs.
将溶剂蒸发后的薄膜分散于水中后，抗坏血酸2,6 -二棕榈酸酯（ASC - DP）与二硬脂酰磷脂酰乙醇胺聚乙二醇2000（DSPE - PEG）以摩尔比小于或等于2:1的比例形成了稳定的纳米颗粒。通过动态光散射测量的平均粒径在约100 - 160nm范围内。利用广角X射线衍射、红外（IR）光谱和固态核磁共振（NMR）光谱分析了薄膜内ASC - DP和DSPE - PEG分子状态随组成的变化。纳米颗粒的透射电子显微镜（TEM）显示，随着摩尔比增加，ASC - DP/DSPE - PEG从胶束结构转变为盘状和管状结构。定量溶液态氢核磁共振测量阐明了纳米颗粒在水中的结构；核心可能由ASC - DP和DSPE的疏水酰基链组成，而表面DSPE - PEG的亲水性PEG链形成水化层以稳定纳米颗粒在水中的分散。通过使用ASC - DP/DSPE - PEG纳米颗粒观察到ASC - DP对癌细胞系的细胞毒性，而未发现对正常细胞的细胞毒性。因此，具有肿瘤细胞特异性细胞毒性的ASC - DP/DSPE - PEG制剂可用于癌症单一疗法或与其他抗癌药物联合使用。
