Therapeutic Effect of Folate-Targeted and PEGylated Phytosomes Loaded with a Mitomycin C-Soybean Phosphatidyhlcholine Complex

被引：38

作者：

Li, Yang ^{[1
,3
]}

Wu, Hongjie ^{[2
]}

Jia, Mengmeng ^{[1
]}

Cui, Fei ^{[1
]}

Lin, Jinyan ^{[1
]}

Yang, Xiangrui ^{[1
]}

Wang, Yange ^{[1
]}

Dai, Lingfeng ^{[1
]}

Hou, Zhenqing ^{[1
]}

机构：

[1] Xiamen Univ, Coll Mat, Dept Biomat & Mat Sci & Engn, Xiamen 361005, Peoples R China

[2] Xiamen Univ, Sch Pharmaceut Sci, Dept Pharm, Xiamen 361005, Peoples R China

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

来源：

MOLECULAR PHARMACEUTICS | 2014年 / 11卷 / 09期

关键词：

mitomycin C; drug delivery; tumor targeting; cancer therapy; phytosomes; ENHANCED ANTITUMOR EFFICACY; LIPID-BASED PRODRUG; DRUG-DELIVERY; PHOSPHOLIPID COMPLEX; IN-VIVO; HYALURONIC-ACID; CANCER-THERAPY; NANOPARTICLES; LIPOSOMES; BIOAVAILABILITY;

D O I：

10.1021/mp5001873

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A mitomycin C (MMC)-soybean phosphatidyhlcholine complex loaded in phytosomes was previously reported for the purpose of developing a MMC drug delivery system (MA Pharmaceutics 2013, 10, 90-101), but this approach was limited by rapid elimination from the body and lack of target specificity. In this article, to overcome these limitations, MMC-soybean phosphatidyhlcholine complex-loaded phytosomes (MMC-loaded phytosomes) as drug carriers were surface-functionalized with folate-PEG (FA-PEG) to achieve reduced toxicity and a superior MMC-mediated therapeutic effect. For this purpose, FA was conjugated to DSPE-PEG-NH2, and the resultant DSPE-PEG-FA was introduced into the lipid moiety of the phytosomes via a postinsertion technique. The prepared FA-PEG-functionalized MMC-loaded phytosomes (FA-PEG-MMC-loaded phytosomes) have a particle size of 201.9 +/- 2.4 nm, a PDI of 0.143 +/- 0.010, a zeta potential of -27.50 +/- 1.67 mV, a spherical shape, and sustained drug release. The remarkable features of FA-PEG-MMC-loaded phytosomes included increased cellular uptake in HeLa cells and higher accumulation in H-22 tumor-bearing mice over that of the PEG-MMC-loaded phytosomes. Furthermore, FA-PEG-MMC-loaded phytosomes were associated with enhanced cytotoxic activity in vitro and an improved antitumor effect in vivo compared to that resulting from free MMC injection. These results suggest that FA-PEG-MMC-loaded phytosomes may be useful drug delivery systems for widening the therapeutic window of MMC in clinical trials.

引用

页码：3017 / 3026

页数：10

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