Li Yang, Lin Jinyan, Wu Hongjie, Jia Mengmeng, Yuan Conghui, Chang Ying, Hou Zhenqing, Dai Lizong
College of Materials, Xiamen University, Xiamen 361005, China.
J Mater Chem B. 2014 Oct 14;2(38):6534-6548. doi: 10.1039/c4tb00499j. Epub 2014 Aug 22.
In the present study we have investigated novel MTX prodrug-targeted and MMC-loaded PLA-lipid-PEG hybrid NPs. These employ a double emulsion solvent evaporation method for the introduction of an anticancer drugs moiety of the MMC-soybean phosphatidylcholine complex or DSPE-PEG-MTX, in which the MTX prodrug can be exploited as a targeting ligand. The prepared drug delivery systems present a spherical shape, a small particle size (219.6 ± 2.1 nm) with narrow particle size distribution, high MMC encapsulation efficiency (90.5 ± 3.0%) and a sustained and pH-controlled MMC release. The advantage of the new drug delivery systems is that the two-anticancer drug moiety can coordinate the early-phase targeting effect with the later-phase anticancer effect. In vivo pharmacokinetics, following intravenous administration of the drug delivery systems, indicates a prolonged systemic circulation time of MMC. More importantly, the drug delivery systems exhibited a significant accumulation of MMC in the nuclei as the site of MMC action, which was indicative of the enhancement of anticancer activity. Such a design of drug delivery systems may open up a new horizon for targeted delivery and sustained and controlled release of MMC.
在本研究中，我们研究了新型甲氨蝶呤（MTX）前药靶向且负载丝裂霉素（MMC）的聚乳酸-脂质-聚乙二醇（PLA-lipid-PEG）杂化纳米粒。这些纳米粒采用双乳液溶剂蒸发法引入MMC-大豆磷脂酰胆碱复合物或二硬脂酰磷脂酰乙醇胺-聚乙二醇-甲氨蝶呤（DSPE-PEG-MTX）的抗癌药物部分，其中MTX前药可作为靶向配体。所制备的药物递送系统呈球形，粒径小（219.6±2.1nm）且粒径分布窄，MMC包封效率高（90.5±3.0%），MMC释放具有持续性且受pH控制。新药物递送系统的优势在于两种抗癌药物部分可将早期靶向作用与后期抗癌作用协同起来。静脉注射药物递送系统后的体内药代动力学表明MMC的全身循环时间延长。更重要的是，药物递送系统在MMC作用部位细胞核中显示出MMC的显著蓄积，这表明抗癌活性增强。这种药物递送系统的设计可能为MMC的靶向递送及持续和控释开辟新的前景。
