Novel methotrexate prodrug-targeted drug delivery system based on PEG-lipid-PLA hybrid nanoparticles for enhanced anticancer efficacy and reduced toxicity of mitomycin C

被引：38
作者：
机构：
[1] College of Materials, Xiamen University, Xiamen
[2] Department of Pharmacy, School of Pharmaceutical Sciences, Xiamen University, Xiamen
[3] Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen
来源：
Hou, Zhenqing | 1600年 / Royal Society of Chemistry卷 / 20期
基金：
中国国家自然科学基金;
关键词：
51;
D O I：
10.1039/c4tb00499j
中图分类号：
学科分类号：
摘要：
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. This journal is © the Partner Organisations 2014.
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页码：6534 / 6548
页数：14
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