Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria , Edificio Polifunzionale, 87036 Arcavacata di Rende, Cosenza, Italy.
Langmuir. 2013 Oct 15;29(41):12638-46. doi: 10.1021/la4021383. Epub 2013 Oct 1.
An efficient tumor-targeted niosomal delivery system for the vehiculation of doxorubicin hydrochloride as an anticancer agent was designed. Niosomes were prepared from a mixture of an opportunely modified Pluronic L64 surfactant and cholesterol as a membrane additive and characterized in terms of size and related distribution function and drug entrapment efficiency. After the preparation, transferrin was conjugated to niosomes to produce transferrin (Tf) niosomes, and the cytotoxicity of the final formulation was studied. The specific uptake of Tf niosomes into cells was evaluated via incubation of MCF-7 and MDA-MB-231 cells with fluorescently rhodamine-loaded Tf niosomes for various times and concentration intervals and further investigated by fluorescence microscopy. Results showed that doxorubicin can be easily encapsulated into niosomes, which are regular and spherical in shape. Moreover, transferrin conjugate niosomes demonstrated far greater extents of cellular uptake by MCF-7 and MDA-MB-231 cells, suggesting that they were mainly taken up by transferrin receptor-mediated endocytosis. Doxorubicin-loaded niosome anticancer activity was also achieved against MCF-7 and MDA-MB-231 tumor cell lines, and a significant reduction in viability in a dose- and time-related manner was observed. Finally, our formulation could be potentially useful as a target doxorubicin delivery system in anticancer therapy.
设计了一种有效的肿瘤靶向脂质体给药系统，用于运载盐酸多柔比星作为抗癌药物。脂质体由一种经过适当修饰的泊洛沙姆 L64 表面活性剂和胆固醇作为膜添加剂的混合物制备而成，并对其大小及相关分布函数和药物包封效率进行了表征。制备后，转铁蛋白被共轭到脂质体上，产生转铁蛋白（Tf）脂质体，并研究了最终制剂的细胞毒性。通过用荧光素 rhodamine 标记的 Tf 脂质体孵育 MCF-7 和 MDA-MB-231 细胞不同时间和浓度间隔，评估 Tf 脂质体对细胞的特异性摄取，并通过荧光显微镜进一步研究。结果表明，多柔比星可以很容易地包封到脂质体中，脂质体呈规则的球形。此外，转铁蛋白缀合脂质体对 MCF-7 和 MDA-MB-231 细胞的摄取程度明显更高，表明它们主要通过转铁蛋白受体介导的内吞作用被摄取。载多柔比星脂质体对 MCF-7 和 MDA-MB-231 肿瘤细胞系也具有抗癌活性，并观察到细胞活力呈剂量和时间依赖性显著降低。最后，我们的制剂可能作为一种有潜力的靶向多柔比星给药系统，用于癌症治疗。
