Zhou Min, Li Xin, Li Yuanyuan, Yao Qiu'e, Ming Yue, Li Ziwei, Lu Laichun, Shi Sanjun
a Department of Pharmacy , Institute of Surgery Research, Daping Hospital/The Third Affiliated Hospital, Third Military Medical University , Chongqing , China.
b Teaching Experimental Center , College of Pharmacy, Third Military Medical University , Chongqing , China.
Drug Deliv. 2017 Nov;24(1):1230-1242. doi: 10.1080/10717544.2017.1370619.
A co-loaded drug delivery system based on ascorbyl palmitate that can transport various functional drugs to their targets within a tumor represents an attractive strategy for increasing the efficiency of anticancer treatment. In this study, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. AP, which is a vitamin C derivative, and PTX were incorporated into solid lipid nanoparticles (AP/PTX-SLNs), which were used to treat murine B16F10 melanoma that had metastasized to the lungs of mice. These nanoparticles were spherical with an average size of 223 nm as measured by transmission electron microscope and dynamic light scattering. In vitro cytotoxicity assays indicated that the AP/PTX-SLNs with an AP/PTX mass ratio of 2/1 provided the optimal synergistic anticancer efficacy. In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs than single drug (AP or PTX)-loaded SLNs via a synergistic effect through reducing the Bcl-2/Bax ratio. Furthermore, no marked side effects were observed during the treatment with the AP/PTX-SLNs, indicating that the co-delivery system with ascorbyl palmitate holds promising clinical potential in cancer therapy.
基于棕榈酸维生素C的共载药物递送系统能够将各种功能性药物输送至肿瘤内的靶点,这是提高抗癌治疗效率的一种有吸引力的策略。在本研究中,我们开发了一种双药物递送系统,用于包封棕榈酸维生素C(AP)和紫杉醇(PTX)以进行协同癌症治疗。AP是一种维生素C衍生物,将其与PTX一起载入固体脂质纳米粒(AP/PTX-SLNs),用于治疗已转移至小鼠肺部的鼠源B16F10黑色素瘤。通过透射电子显微镜和动态光散射测量,这些纳米粒呈球形,平均尺寸为223nm。体外细胞毒性试验表明,AP/PTX质量比为2/1的AP/PTX-SLNs具有最佳的协同抗癌效果。在体内,通过降低Bcl-2/Bax比率产生协同效应,与载单一药物(AP或PTX)的SLNs相比,AP/PTX-SLNs在抑制荷B16F10小鼠肿瘤生长以及消除肺部癌细胞方面更有效。此外,在用AP/PTX-SLNs治疗期间未观察到明显的副作用,这表明含有棕榈酸维生素C的共递送系统在癌症治疗中具有广阔的临床应用前景。