Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells.
Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells.
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基于微乳的协同双药共递送系统增强肿瘤细胞凋亡
DOI：
10.2147/ijn.s76742
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发表时间：
2015
影响因子：
8
通讯作者：
Huang M
中科院分区：
文献类型：
--
作者：
Qu D;Ma Y;Sun W;Chen Y;Zhou J;Liu C;Huang M
开发了一种基于微乳的协同双药共递送系统，通过将薏苡仁油和依托泊苷同时转运至 A549（人肺癌）细胞中来增强细胞凋亡。动态光散射结果表明，负载依托泊苷（VP16）的薏苡仁油微乳（EC-ME）递送系统粒径小，约为35 nm，多分散指数窄，表面带轻微负电荷。高效液相色谱测定包封率和总载药量分别为97.01%和45.48%。不同pH值下的释放曲线显示出明显的pH响应差异，在pH 4.5（和pH 5.5）下VP16的累积释放量相对于pH 7.4时高出2.7倍。透射电子显微镜发现与弱酸性 pH 环境相关的形态改变（颗粒膨胀）。在细胞研究中，与游离VP16以及VP16和薏苡仁油的混合物相比，EC-ME系统对A549细胞显示出显着更强的抗增殖作用。 EC-ME系统的半最大抑制浓度分别比游离VP16和VP16与薏苡仁油的混合物低3.9倍和10.4倍。此外，通过直观观察和定量测量，异硫氰酸荧光素和VP16（分别为绿色荧光探针和包埋药物）通过薏苡仁油微乳液有效地内化到细胞内。重要的是，与负载 VP-16 的微乳液和游离 VP16 相比，含有 20 μg/mL VP16 的 EC-ME 系统在诱导细胞凋亡方面分别表现出 3.3 倍和 3.5 倍的改善。 EC-ME 组合策略有望成为诱导细胞凋亡和治疗肺癌的有效药物递送系统。
A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 μg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer.