School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Drug Dev Ind Pharm. 2012 Sep;38(9):1134-41. doi: 10.3109/03639045.2011.641565. Epub 2011 Dec 19.
The purpose of this study was to investigate preparation, characterization and tumor-targeted effect of pH-sensitive niosomes, composed of a nonionic surfactant mixed with cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol (CHOL), as a pH-sensitive molecule. CHEMS was synthesized with CHOL and succinic acid, the structure of which was analyzed by Mass spectrometry (MS) and ¹H Nuclear magnetic resonance (¹H NMR) spectrum. Niosomes were prepared via film hydration-probe ultrasound method. Both normal niosomes and pH-sensitive niosomes showed spherical morphology under transmission electron microscope (TEM) with a average particle sizes of 172 ± 6.2 nm and 153 ± 4.7 nm, respectively. The thermotropic behavior, structure changes and interaction of 5-fluorouracil (5-Fu) with other materials were characterized by differential scanning calorimetry (DSC), and the disappearance of the melting peak of drug revealed the fact that drug was encapsulated in niosomes. Bulk-equilibrium reverse-dialysis method was chosen to investigate the behavior of drug release from normal niosomes and pH-sensitive niosomes in different pH medium, and the results showed that the noisome containing CHEMS had a pH-sensitive property. Tumor-targeted effect was proved by the fact that pH-sensitive niosomes showed a remarkable high concentration in tumor site of the mice transplanted with tumor cell.
本研究旨在探讨由非离子表面活性剂与胆甾醇半琥珀酸酯（CHEMS）组成的 pH 敏感型脂质体的制备、表征和肿瘤靶向效果。CHEMS 是由胆甾醇（CHOL）和琥珀酸合成的，其结构通过质谱（MS）和 ¹H 核磁共振（¹H NMR）谱进行分析。采用薄膜水化探头超声法制备脂质体。透射电子显微镜（TEM）下，正常脂质体和 pH 敏感脂质体均呈现出球形形态，平均粒径分别为 172±6.2nm 和 153±4.7nm。差示扫描量热法（DSC）用于表征 5-氟尿嘧啶（5-Fu）与其他物质的热行为、结构变化和相互作用，药物的熔融峰消失表明药物被包封在脂质体中。采用体积平衡反向透析法研究了不同 pH 介质中正常脂质体和 pH 敏感脂质体中药物释放的行为，结果表明含有 CHEMS 的脂质体具有 pH 敏感性。通过在移植肿瘤细胞的小鼠肿瘤部位观察到 pH 敏感脂质体具有显著的高浓度，证明了其具有肿瘤靶向效果。
