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：1

作者：

Li, Yang ^{[1
,3
]}

Lin, Jinyan ^{[1
]}

Wu, Hongjie ^{[2
]}

Jia, Mengmeng ^{[1
]}

Yuan, Conghui ^{[1
]}

Chang, Ying ^{[1
]}

Hou, Zhenqing ^{[1
]}

Dai, Lizong ^{[1
]}

机构：

[1] Xiamen Univ, Coll Mat, Xiamen 361005, Peoples R China

[2] Xiamen Univ, Sch Pharmaceut Sci, Dept Pharm, Xiamen 361002, Peoples R China

[3] Xiamen Univ, Coll Chem & Chem Engn, Dept Chem, Xiamen 361005, Peoples R China

来源：

JOURNAL OF MATERIALS CHEMISTRY B | 2014年 / 2卷 / 38期

基金：

中国国家自然科学基金;

关键词：

PH-SENSITIVE LIPOSOMES; SMALL INTERFERING RNA; IN-VIVO; COPOLYMER NANOPARTICLES; PEGYLATED LIPOSOMES; ANTITUMOR EFFICACY; TUMOR-CELLS; CANCER; GLYCOPROTEIN; PACLITAXEL;

D O I：

10.1039/C4TB00499J

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

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.

引用

页码：6534 / 6548

页数：15